Statins are widely used to treat hyperlipidemia and atherosclerotic cardiovascular diseases (ACVD) by significantly lowering low-density lipoprotein cholesterol (LDL-C) levels. However, their use has been associated with an increased risk of type 2 diabetes (T2D), a paradox given their lipid-lowering benefits. This study investigates the role of LDL receptors (LDLR) and proprotein convertase subtilisin/kexin type 9 (PCSK9) in the diabetogenic effects of atorvastatin on pancreatic β-cells. Using the MIN6 pancreatic β-cell line, we assessed the impact of atorvastatin on LDL-C uptake, PCSK9 expression, glucose-stimulated insulin release (GSIR), and cell proliferation. Cellular cholesterol assays, EdU labeling, Dil-LDL uptake, western blot analysis, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and ELISA, were employed to measure relevant biomarkers and cellular responses. Male C57BL/6j mice were treated with atorvastatin to validate in vitro findings. Atorvastatin enhances LDL-C uptake by upregulating LDLR on the cell surface, without causing excess cholesterol accumulation. Additionally, atorvastatin suppresses PCSK9 expression, which is crucial for LDLR degradation. Interestingly, atorvastatin, combined with exogenous LDL-C, impairs glucose-stimulated insulin release (GSIR) but promotes cell proliferation, highlighting a potential mechanism for statin-associated diabetes. Oral administration of atorvastatin in mice reduced plasma PCSK9 and insulin levels, supporting the in vitro findings. These results indicate that while atorvastatin effectively lowers circulating cholesterol, it may adversely affect pancreatic β-cell function by modulating LDLR and LDL-C uptake, thereby increasing the risk of T2D. This study highlights the importance of further research to develop strategies mitigating the diabetogenic effects of statins while maintaining their cardiovascular benefits.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in patients with chronic kidney disease (CKD). Quantitative and qualitative changes in plasma lipoprotein profiles are frequently associated with CKD and represent a significant risk factor for CVD in patients with CKD. Guidelines from the European Society of Cardiology and the European Atherosclerosis Society classify CKD as a condition with high or very high cardiovascular risk and set specific low-density lipoprotein cholesterol targets. Conventional lipid-lowering therapies (LLTs), such as statins, ezetimibe, and fibrates, can control CKD-associated dyslipidemia and, to some extent, prevent major atherosclerotic events in patients with CKD, but their use in clinical practice presents challenges because of the potential renal safety concerns. In recent years, novel therapies with the ability to lower both low-density lipoprotein cholesterol and triglycerides have been introduced to the market (e.g., proprotein convertase subtilisin/kexin type 9 inhibitors, bempedoic acid, lomitapide, volanesorsen) to improve our ability to control lipid abnormalities. However, their impact on kidney functionality has not been fully elucidated. The aim of this review was to examine the renal safety profiles of various LLTs, with special reference to novel medications, and to highlight important considerations and guidance for the use of these medications in overt CKD or in patients with some degree of renal function impairment. We underscore the lack of a comprehensive understanding of kidney safety, particularly for novel LLT therapies, and strongly emphasize the importance of future dedicated research to fully assess the safety and efficacy of these agents in patients with kidney abnormalities.

Polycystic ovary syndrome (PCOS) represents the most prevalent endocrine disorder among women of reproductive age, affecting approximately 5-18% of females worldwide. Characterized by irregular ovulation, hyperandrogenism, and polycystic ovaries, hyperandrogenism is the defining feature. Recent evidence highlights that, in addition to its notable reproductive and metabolic consequences, PCOS may also contribute to an elevated risk of renal complications. This increased risk is attributed to chronic low-grade inflammation, hormonal dysregulation, and disturbances in lipid metabolism inherent to the condition. However, the pathological mechanisms, clinical manifestations, and progression of secondary renal damage in this cohort remain insufficiently studied. This review consolidates current understanding of the relationship between PCOS and chronic kidney disease (CKD), aiming to clarify potential mechanisms by which PCOS may induce secondary renal dysfunction, encompassing both direct renal impairment and indirect damage mediated through systemic alterations. Furthermore, it advocates for comprehensive management strategies to mitigate renal risks in patients with PCOS, emphasizing the necessity of multidisciplinary approaches and further research to address these critical gaps.

Dyslipidemic statins reduce blood and brain cholinesterase (ChE) activities in mice, with scarce information on other protein/enzyme targets. The study aims at conducting a mini meta-analysis on in vivo and in vitro adverse anti-ChE effects of atorvastatin, simvastatin and rosuvastatin in mice, and using the SwissPrediction to identify in silico body target proteins. The data comprised 72 records of plasma, erythrocytes and brain ChE activities, expressed as percent mean ± SD of respective controls. We conducted a randomized effects size single-arm meta-analysis. The risk of bias scoring was according to those of animal experiments. The effect size (% ChE activity) of statin treatments was significantly decreased by 25.85 % (combined effect size=74.15, p = 0.0001), with significant heterogeneity (Q=1133.19, p < 0.0001, I2=93.73 %). Subgroup analysis was significantly dose and concentration-dependent. The funnel plot showed non-symmetrical data distribution, with no imputed points. The risk of bias was moderate. In silico mouse body protein targets for the statins were mainly classes of Family AG protein- coupled receptor (20.0 %-33.3 %), Oxidoreductase (6.7-13.3 %) and Eraser (13.3 % each), with others at 0-26.7 %. The findings highlight statin effects in mice by reducing blood and brain ChE activities, in a dose/concentration-dependent manner, that would potentially modulate the cholinergic system. This anti-ChE effect together with in silico protein targets recognized could be the basis of further experimental explorations of adverse effects of statins.

People living with HIV (PLWH) are more vulnerable to cerebrovascular disease, including coronary artery disease. Dyslipidemia is a risk factor for major adverse cardiovascular events in this population as a whole. Dyslipidemia might result from general risk factors, HIV itself, or the adverse effects of the antiretroviral drug, which have different effects on lipid profile. The present study aims to review the latest studies regarding the role of statin initiation in this population and clinically significant drug interactions in the field.

Databases, including Scopus, PubMed, Google Scholar, EMBASE, and Web of Science, were searched for relevant literature on the role of statins in primary/secondary prevention of CVD in PLWH based on the PICO search strategy. Moreover, ARTs-statin drug interactions were investigated and summarized based on the University of Liverpool's website.

Nearly 70 studies were found and summarized. Guidelines recommendations for using statins in PLWH and current practice, as well as the role and potential mechanism of statins in PLWH, were investigated. Based on the available data, we developed a practical algorithm that clinicians can use to optimize statin therapy in PLWH.

More studies are required to fully define the role of statins in HIV patients, including time to initiate and proper dosing. Moreover, a marked inconsistency exists between clinical guidelines and actual practice, mainly due to irrational concerns regarding antiretroviral-statin drug interactions.

Coenzyme Q10 is a natural antioxidant with anti-tumor and mitochondrial protective effects. However, its unstable physicochemical properties and large molecular weight result in low bioavailability. This study aimed to develop an effective technique for constructing nanoliposomes to improve the physicochemical properties of CoQ10 by using high-pressure microfluidic homogenization. Liposomes were prepared using the ethanol injection method and homogenized by high-pressure microfluidics to optimize their physicochemical properties. Liposome morphology and microstructure were observed via transmission electron microscopy (TEM). The particle size distribution, polydispersity index (PDI), and encapsulation efficiency were assessed, while effects on cell viability and antioxidant properties were investigated in HepG2 cells. The results indicate that the prepared liposomes exhibit favorable characteristics, including high encapsulation efficiency (>96%) and low PDI (<0.3), indicating uniform particle size distribution and good stability. The storage stability of liposomes at room temperature was significantly enhanced compared to liposomes not subjected to high pressure homogenization. In vitro cell experiments confirmed the liposomes' non-cytotoxicity and substantial antioxidant activity, ensuring their safety for biomedical applications. This study introduced a liposome preparation method combining ethanol injection and high-pressure microfluidic homogenization, offering a novel approach for liposome modification with potential for development and application in innovative drug delivery systems and antioxidant therapy.

Chemotherapy-induced cardiomyopathy (CICM) is a critical adverse consequence associated with chemotherapeutic treatments such as anthracyclines, taxanes, and alkylating agents. Cardiac dysfunction, characterized by left ventricular systolic dysfunction, is the primary effect found in these patients. This may result in heart failure, with heart failure related to chemotherapy resulting in a 3.5-fold increased risk of mortality compared with idiopathic cardiomyopathy alone. Multiple factors, including oxidative stress, inflammation, and disruption of key cellular pathways, are involved in cardiomyocyte damage and influence CICM pathophysiology. So far, dexrazoxane is the sole FDA-approved preventive therapy, but alternative interventions, such as beta-blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and statins, have been studied for their cardioprotective potential. Statins, beyond their cholesterol-lowering capabilities, stand out for their pleiotropic effects, including antioxidant, anti-inflammatory, and endothelial-protective actions, which counteract inflammatory effects. Multiple studies and meta-analyses suggest that statin therapy may decrease both the incidence and severity of chemotherapy-related cardiotoxicity (CTX), as evidenced by smaller declines in left ventricular ejection fraction and lower rates of heart failure in statin-treated patients. However, not all investigations confirm these protective benefits; for instance, some trials, including SPARE-HF, reported no significant differences in cardiac outcomes. While these conflicting findings underscore the need for larger randomized trials, they also reflect the heterogeneity of cancer types, chemotherapy regimens, and patient profiles. Statins show promise as a cardioprotective strategy for individuals at risk of CICM. Enhancing patient selection and specifying the timing and duration of statin therapy are essential steps for incorporating these agents into standard care. Optimizing these parameters may reduce chemotherapy-related cardiac damage, improve long-term cardiac function, and enhance overall survival in cancer survivors.

Statins have been reported for diverse pleiotropic activities, including antimicrobial and antibiofilm. However, due to the limited understanding of their mode of action, none of the statins have gained approval for antimicrobial or antibiofilm applications. In a recent drug repurposing study, we observed that two statins (i.e., Simvastatin and Lovastatin) interact stably with TasA(28-261), the principal extracellular matrix protein of Bacillus subtilis, and also induce inhibition of biofilm formation. Nevertheless, the underlying mechanism remained elusive. In the present study, we examined the impact of these statins on the physiological activity of TasA(28-261), specifically its interaction with TapA(33-253) and aggregation into the amyloid-like structure using purified recombinant TasA(28-261) and TapA(33-253) in amyloid detection-specific in vitro assays (i.e., CR binding and ThT staining assays). Results revealed that both statins interfered with amyloid formation by the TasA(28-261)-TapA(33-253) complex, while neither statin inhibited amyloid formation by lysozyme, a model amyloid-forming protein. Moreover, neither statin significantly altered the expressions of terminal regulatory genes (viz, sinR, sinI) and terminal effector genes (viz, tasA, tapA, and bslA) involved in biofilm formation by B. subtilis. While the intricate interplay between Simvastatin and Lovastatin with the diverse molecular constituents of B. subtilis biofilm remains to be elucidated conclusively, the findings obtained during the present study suggest that the underlying mechanism for Simvastatin- and Lovastatin-mediated inhibition of B. subtilis biofilm formation is manifested by interfering with the aggregation and amyloid formation by TasA(28-261)-TapA(33-253). These results represent one of the first experimental evidence for the underlying mechanism of antibiofilm activity of statins and offer valuable directions for future research to harness statins as antibiofilm therapeutics.

Recent studies have highlighted the importance of cross-talk along the gut-brain axis in regulating inflammatory nociception, inflammatory responses, and immune homeostasis. The gut microbiota, particularly its bacterial composition, plays a crucial role in the development and function of the immune system. Moreover, metabolites produced by the gut microbiota can significantly impact both systemic immune responses and central nervous system (CNS) immunity. Sodium butyrate is a key metabolite produced by the gut microbiota and, as a histone deacetylase inhibitor, can enhance the anti-tumor immunity of cytotoxic CD8+ T cells. However, it remains unclear whether sodium butyrate treatment can enhance the efficacy of PD-1 blockade in glioma therapy. In this research, the effect and underlying mechanism of combination of gut microbiota metabolites and anti-mouse PD-1 mAb on glioma has been investigated.

RNA-seq assay in glioma cell and biomedical databases, including ONCOMINE, GEPIA and TCGA were incorporated. Subsequently, the inhibitory effect of sodium butyrate on glioma cells and its related mechanisms were assessed through Counting Kit-8 (CCK-8), Flow Cytometry, Western blot (WB), reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and other in vitro experiments. In vitro, an orthotopic mouse glioma model was established. MRI imaging, Immunohistochemistry, and Immune cell flow cytometry were used to investigate the therapeutic effects of combined sodium butyrate and PD-1 inhibitor treatment on glioma-bearing mice.

We discovered that deacetylation-associated gene expression is significantly increased in glioma patients and affects patient survival time. Moreover, we found sodium butyrate promoted glioma cell apoptosis, disrupted the cell cycle, and inhibited tumor growth. Additionally, sodium butyrate may upregulate PD-L1 expression in glioma cells by modulating the PI3K/AKT pathway. The experimental results demonstrated that this combination therapy significantly reduced tumor volume and prolonged survival in an orthotopic murine glioma model. Moreover, combination therapy led to an increase in the proportion of probiotic bacteria in the mouse gut microbiota, resulting in elevated levels of antitumor metabolites and a decrease in metabolites that affect immune cell function.

This study aimed to systematically evaluate the efficacy of electroacupuncture and manual acupuncture for treating vascular dementia and to determine the optimal acupuncture point combination scheme for efficacy.

The PubMed, Embase, Web of Science, Cochrane, CNKI, VIP, and Wanfang electronic databases were searched up to July 2024 to identify relevant randomized controlled trials. RevMan 5.4 software and Addis software were used to assess the risk of bias for each study, determine subgroup classifications, and conduct meta-analyses.

A total of 29 RCTs involving 659 animals were ultimately included. The meta-analysis results revealed that acupuncture treatment had a significant effect compared with the vascular dementia model group [mean difference (MD) = - 21.68, 95% confidence interval (CI) (- 25.77, - 17.59), P < 0.00001]. Manual acupuncture demonstrated better efficacy than electroacupuncture did [MD = - 0.42, 95% CI (- 12.72, 12.27)]. Among the different acupuncture point combinations, the Baihui (GV20) + Dazhui (GV14) combination yielded the best efficacy [MD = - 23.03, 95% CI (- 30.02, - 16.04), P < 0.00001]. Compared with other acupuncture protocols, the experiment conducted by Caiyu Peng et al. exhibited superior efficacy [MD = - 24.96, 95% CI (- 92.68, - 40.76)].

Acupuncture significantly improves cognitive function in rats with vascular dementia. Manual acupuncture is more effective than electroacupuncture. Among the different acupuncture point combinations, manual acupuncture at GV20 and GV14 yields the best results. Compared with other acupuncture protocols, the best efficacy was observed when the two-vessel occlusion (2VO) model was used in 230 ± 10 g SD rats; when the Mingmen (GV4), Dazhui (GV14), Fengfu (GV16), Baihui (GV20), Shenting (GV24), Shuigou (GV26), Neiguan (PC6), Dalin (PC7), and Laogong (PC8) acupoints were selected; and when manual acupuncture with reinforcing and reducing methods was used for 30 min per day for 14 days.

PROSPERO CRD42024551402.

Placentation is a key process that is tightly regulated that ensures the normal placenta and fetal development. Preeclampsia (PE) is a hypertensive pregnancy‑associated disorder characterized by increased oxidative stress and inflammation. STAT3 signaling plays a key role in modulating important processes such as cell proliferation, differentiation, invasion and apoptosis. The present review aimed to analyse the role of STAT3 signaling in PE pregnancies, discuss the main natural and synthetic compounds involved in modulation of this signaling both in vivo and in vitro and summarize the main cellular modulators of this signaling to identify possible therapeutic targets and treatments to improve the outcome of PE pregnancies.

The brain is the most cholesterol-rich organ, essential for myelination and neuronal function. Statins, widely used to lower cholesterol, cross the blood-brain barrier and may impact brain cholesterol synthesis. Despite their widespread use, the effects of statins on cortical regions relevant to Alzheimer's disease (AD) are not well understood. This study aimed to compare cortical thickness between statin-exposed and statin-unexposed older adults and evaluate the potential neuroprotective effects of statins.

Data were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The sample included 193 healthy controls (HC), 485 individuals with mild cognitive impairment (MCI), and 169 individuals with Alzheimer's disease (AD). Participants were categorized as statin users if they had used statins for at least two years. MRI data were processed using FreeSurfer software to estimate cortical thickness in 64 regions of interest. ANCOVA models assessed the association between statin use and cortical thickness at baseline, and linear mixed models evaluated longitudinal changes.

Statin use was associated with increased cortical thickness in multiple brain regions across HC, MCI, and AD participants. In HC, statin users had greater thickness in the right lateral occipital, left middle temporal, and left parahippocampal regions. MCI participants exhibited additional increases in the right cuneus, right posterior cingulate, and left superior temporal cortex. In AD, statin users had higher thickness in the right cuneus and right superior parietal lobule. Longitudinal analysis revealed no statin-related differences in cortical thickness changes among HC and AD groups, but in MCI, statins slowed cortical thinning in the left medial orbitofrontal cortex.

Statin use is associated with greater cortical thickness in older adults, particularly in those with MCI. These findings suggest that statins may have neuroprotective effects, potentially mitigating neurodegenerative changes in early cognitive decline. Further research with larger cohorts and longer follow-up periods is needed to confirm these findings and understand the mechanisms involved.

This meta-analysis delved into the impact of statin therapy, both as a monotherapy and in conjunction with antihypertensive medications, on blood pressure levels and outcomes pertinent to hypertension.

We searched the PubMed, EMBASE, and Cochrane databases for studies published before October 1 2023. Studies designed as cohort studies or randomized controlled trials and investigating the effects of single use of statin or its combined use with other antihypertensive therapy were included. Authors extracted the data independently and differences were decided through discussion. Random-effects model was used to evaluate the merged outcomes. Due to the high heterogeneity of the HDL-C group, we performed subgroup analysis according to the type of statin. To assess the robustness and potential publication bias of our findings, we utilized sensitivity analysis, Egger's test, and funnel plots.

23 trials were included in this meta-analysis. The primary outcomes revealed that administering statins did not significantly impact the systolic pressure (SBP) of hypertensive patients (MD, -1.77; 95 % CI, -4.82-1.27). -The promoted effect of statin treatment on diastolic pressure (DBP) in hypertensive patients was found (MD, -1.87; 95 % CI, -3.72 --0.01). The secondary outcomes revealed that the use of statins resulted in a significant reduction in low-density lipoprotein (LDL-C), while significantly increasing high-density lipoprotein (HDL-C) in hypertensive patients.

Statin use did not modulate SBP and DBP of patients with hypertension, but SBP was decreased in the rosuvastatin or pravastatin subgroup, while DBP was decreased in the simvastatin or pravastatin subgroup. Statin treatment reduced LDL-C, increased HDL-C, and reduced the incidence of cardiovascular events and mortality compared to control groups.

Background/Objectives: Atorvastatin (ATR), an antihyperlipidemic drug with a potential antibacterial effect, was investigated in this study. Like other statins, ATR has been repurposed for several uses, ranging from anti-inflammatory to antimicrobial applications, and has demonstrated successful results. However, the efficacy of ATR is limited by its low solubility, indicating an opportunity for its encapsulation in a nanotechnology-based drug delivery system. Methods: Nanostructured lipid carrier (NLC) formulations were prepared using high-pressure homogenization and ultrasonication. The formulations were characterized, including their particle size, polydispersity index, zeta potential, encapsulation efficiency, and in vitro release. Antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli (E. coli), and Staphylococcus aureus (S. aureus) was evaluated using the growth curve (bacterial growth over time) and well diffusion methods (zone of inhibition and minimum inhibitory concentration (MIC) determination). The crystal violet assay was employed to assess biofilm inhibition. Results: The NLC formulations were optimized, and the size and zeta potential of the blank nanoparticles were 130 ± 8.39 nm and -35 ± 0.5 mV, respectively. In comparison, the encapsulated NLCs had a size of 142 ± 52.20 nm and a zeta potential of -31 ± 1.41 mV. The average encapsulation efficiency was 94%, and 70% of the drug was released after 24 h. The ATR-loaded NLCs showed significantly enhanced antibacterial activity by reducing the minimum inhibitory concentration by 2.5-fold for E. coli, 1.8-fold for S. aureus, and 1.4-fold for MRSA, and promoting more effective bacterial growth inhibition. Notably, biofilm inhibition was significantly improved with ATR-NLCs, achieving 80% inhibition for S. aureus, 40% for E. coli, and 30% for MRSA, compared to free ATR (p < 0.001). These findings suggest that NLC encapsulation enhances ATR's antimicrobial efficacy and biofilm suppression. Conclusions: This study identified NLCs as successful carriers of ATR, significantly enhancing its antibacterial efficacy and biofilm inhibition capabilities. This formulation, which shows antimicrobial potential against both Gram-positive and Gram-negative bacteria, should be further studied and developed against different resistant microbial strains.

Colorectal cancer (CRC) poses a significant clinical challenge because of drug resistance, which can adversely impact patient outcomes. Recent research has shown that abnormalities within the tumor microenvironment, especially hyperglycemia, play a crucial role in promoting metastasis and chemoresistance, and thereby determine the overall prognosis of patients with advanced CRC.

This study employs data mining and consensus molecular subtype (CMS) techniques to identify pitavastatin and atorvastatin as potential agents for targeting high glucose-induced drug resistance in advanced CRC cells. CRC cells maintained under either low or high glucose conditions were established and utilized to assess the cytotoxic effects of pitavastatin and atorvastatin, both with and without 5-fluorouracil (5-FU). CRC 3D spheroids cultured were also included to demonstrate the anti-drug resistance of pitavastatin and atorvastatin.

A bioinformatics analysis identified pitavastatin and atorvastatin as promising drug candidates. The CMS4 CRC cell line SW480 (SW480-HG) was established and cultured under high glucose conditions to simulate hyperglycemia-induced drug resistance and metastasis in CRC patients. Pitavastatin and atorvastatin could inhibit cell proliferation and 3D spheroid formation of CMS4 CRC cells under high glucose conditions. In addition, both pitavastatin and atorvastatin can synergistically promote the 5-FU-mediated cytotoxic effect and inhibit the growth of 5-FU-resistant CRC cells. Mechanistically, pitavastatin and atorvastatin can induce apoptosis and synergistically promote the 5-FU-mediated cytotoxic effect by activating autophagy, as well as the PERK/ATF4/CHOP signaling pathway while decreasing YAP expression.

This study highlights the biomarker-guided precision medicine strategy for drug repurposing. Pitavastatin and atorvastatin could be used to assist in the treatment of advanced CRC, particularly with CMS4 subtype CRC patients who also suffer from hyperglycemia. Pitavastatin, with an achievable dosage used for clinical interventions, is highly recommended for a novel CRC therapeutic strategy.

Aberrant lipid metabolism is a well-recognized hallmark of cancer. Notably, breast cancer (BC) arises from a lipid-rich microenvironment and depends significantly on lipid metabolic reprogramming to fulfill its developmental requirements. In this review, we revisit the pivotal role of lipid metabolism in BC, underscoring its impact on the progression and tumor microenvironment. Firstly, we delineate the overall landscape of lipid metabolism in BC, highlighting its roles in tumor progression and patient prognosis. Given that lipids can also act as signaling molecules, we next describe the lipid signaling exchanges between BC cells and other cellular components in the tumor microenvironment. Additionally, we summarize the therapeutic potential of targeting lipid metabolism from the aspects of lipid metabolism processes, lipid-related transcription factors and immunotherapy in BC. Finally, we discuss the possibilities and problems associated with clinical applications of lipid‑targeted therapy in BC, and propose new research directions with advances in spatiotemporal multi-omics.

3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) inhibitors, commonly known as statins, are drugs frequently used in the treatment of hypercholesterolemia and hyperlipidemia. However, the current study has demonstrated that simvastatin induces neurotoxicity and is associated with cellular coenzyme Q10 (CoQ10) depletion. CoQ10 has a significant role in the mitochondrial electron transport chain (ETC), in addition to being a fundamental lipid-soluble antioxidant. Depletion of CoQ10 is frequently associated with impaired mitochondrial function and increased oxidative stress. The aim of this study was to investigate the potential mechanisms of simvastatin-induced neurotoxicity assessing mitochondrial function and evidence of oxidative stress in an in vitro SH-SY5Y human neuronal cell line. Fluorescence studies assessed via flow cytometry determined significant increases in intracellular and mitochondrial reactive oxygen species production following SH-SY5Y treatment with simvastatin compared to control cells. Additionally, spectrophotometric enzyme studies determined a significant (p < 0.0001) inhibition of ETC complex I and II-III activities which accompanied a significant decrease in neuronal CoQ10 content (p < 0.005) and cell viability (p < 0.0001). The results of the present study have indicated evidence of mitochondrial dysfunction and increased oxidative stress, resulting in increased loss of neuronal viability following simvastatin treatment. Thus, these results demonstrate evidence of neurotoxicity associated with statin therapy.

Background: It remains unclear whether cholesterol-lowering therapy can reduce the incidence of microvascular complications in patients with diabetes. We aim to explore the potential causal relationship between three common types of cholesterol-lowering drugs and diabetic microvascular complications through drug-target Mendelian randomization (MR) study, laying the groundwork for the development of new medications. Methods: In this study, we collected single nucleotide polymorphisms (SNPs) associated with HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) inhibitors, PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors, and NPC1L1 (Niemann-Pick C1-Like 1) inhibitors from published genome-wide association study statistics. Subsequently, drug-target MR analyses were performed to investigate the effects of these inhibitors on low-density lipoprotein cholesterol (LDL-C) level-mediated microvascular complications in diabetes mellitus. Coronary atherosclerosis as a positive control. Primary outcomes included diabetic nephropathy, diabetic retinopathy, and diabetic neuropathy from the FinnGen Consortium. Results: The MR analysis revealed significant associations between HMGCR inhibition and increased risks of diabetic nephropathy (OR [95%confidence interval (CI)] = 1.88 [1.50, 2.36], p = 5.55 × 10-8), retinopathy (OR [95%CI] = 1.86 [1.54, 2.24], p = 6.28 × 10-11), and neuropathy (OR [95%CI] = 2.63 [1.84, 3.75], p = 1.14 × 10-7) using the inverse variance weighted method. PCSK9 inhibitors have been associated with an increased risk of diabetic nephropathy (OR [95%CI] = 1.30 [1.07, 1.58], p = 0.009) and diabetic neuropathy (OR [95%CI] = 1.40 [1.15, 1.72], p = 0.001); NPC1L1 inhibitors significantly reduce the incidence of diabetic retinopathy (OR [95%CI] = 0.48 [0.28, 0.85], p = 0.01). The coronary heart disease as positive control. Conclusions: The findings show that HMGCR inhibitors and PCSK9 inhibitors may significantly increase the risk of diabetic microvascular complications. However, NPC1L1 inhibitors may provide protection against diabetic retinopathy.

Two single nucleotide polymorphisms (SNPs) in the human SLCO1B1 gene, c.388A>G (rs2306283) and c.521T>C (rs4149056), are independent determinants of the efficacy and side effects of statin drugs. Multinational clinical guidelines recommend testing for SLCO1B1 genotypes before the initial use of statins. Current SLCO1B1 SNP identification methods, primarily based on quantitative fluorescence PCR, rely on expensive equipment, are time-consuming, and require cold-chain storage for reagents, making them unsuitable for use in resource-limited healthcare settings. In this study, we developed a CRISPR/Cas12b-based amplification-free genotyping technique for SLCO1B1 SNPs. Within 30 minutes of the isothermal reaction, genotyping of the c.388A>G and c.521T>C SNPs in the SLCO1B1 gene can be observed by the naked eyes under blue light. Additionally, maltodextrin was identified as an effective vitrification stabilizer for the CRISPR/Cas12b premix. A low-cost vitrification process was optimized to prepare a glass like solid reagent via room-temperature vacuum drying. The vitrified CRISPR/Cas12b reagent retained approximately 88% of its activity after 30 days of storage at 37 °C, eliminating the need for cold-chain storage and allowing for long-term preservation at room temperature. This vitrified CRISPR/Cas12b based rapid SNP detection technique is especially suitable for genotyping drug metabolism genes in primary healthcare settings, providing effective guidance for precision medicine in clinical practice.

Peritoneal dialysis (PD) is considered a life-saving treatment for end-stage renal disease. However, prolonged PD use can lead to the development of peritoneal fibrosis (PF), diminishing its efficacy. Peritoneal mesothelial cells (PMCs) are key initiators of PF when they become damaged. Exposure to high glucose‑based peritoneal dialysis fluids (PDFs) contributes to PF development by directly affecting highly metabolically active PMCs. Recent research indicates that PMCs undergo metabolic reprogramming when exposed to high-glucose PDFs, including enhanced glycolysis, impaired oxidative phosphorylation, abnormal lipid metabolism, and mitochondrial dysfunction. Although this metabolic transition temporarily compensates for the cellular damage and maintains energy levels, its long-term impact on peritoneal tissue is concerning. Multiple studies have identified a close association between this shift in energy metabolism and PF, and may promote the progression of PF through various molecular mechanisms. This review explores recent findings regarding the role and mechanism of PMC metabolic reprogramming in PF progression. Moreover, it provides a summary of potential therapeutic strategies aimed at various metabolic processes, including glucose metabolism, lipid metabolism, and mitochondrial function. The review establishes that targeting metabolic reprogramming in PMCs may be a novel strategy for preventing and treating PD-associated fibrosis.

There was considerable debate regarding the effect of statins administration on the outcome of septic patients. This retrospective study aimed to assess the association between statins administration and mortality in sepsis patients and investigate whether this association differed according to the types of statins.

We performed a retrospective study based on the electronic ICU Collaborative Research Database, Medical Information Mart for Intensive Care Database, and the Amsterdam University Medical Centers Database. The participants with sepsis were divided as two groups, statins group and non-statins group. The primary endpoint was the all-cause mortality. We utilized logistic regression, propensity score matching (PSM), and sub-analysis to assess the association between statins administration and outcome in patients with sepsis.

A total of 19,327 sepsis patients were enrolled. Among these, 3,721 patients were prescribed statins. Pooled analyses of three databases showed that statin users had a decreased risk of mortality in sepsis as compared with nonusers (OR 0.73, 95% CI 0.66-0.80, P < 0.001). Sub-analysis of statin showed that atorvastatin had the most distinct effectiveness in decreasing mortality (OR 0.67, 95% CI 0.59-0.76, P = 0.035), whereas pravastatin, simvastatin, and rosuvastatin were not. PSM analysis confirmed these findings for statins (OR 0.75, 95% CI 0.67-0.84, P < 0.001) and atorvastatin (OR 0.70, 95% CI 0.59-0.82, P < 0.001).

The use of statins could decrease the risk of mortality in patients with sepsis during the hospital period. Among different types of statins, atorvastatin showed the most significant trend to reduce the risk of mortality in patients with sepsis.

Non-alcoholic fatty liver disease (NAFLD) is a common hepatic manifestation of metabolic syndrome affecting 20-30 % of the adult population worldwide. This disease, which includes simple steatosis and non-alcoholic steatohepatitis, poses a significant risk for cardiovascular and metabolic diseases. Lifestyle modifications are crucial in the treatment of NAFLD; however, patient adherence remains challenging. As there is no specific treatment, drug repositioning is being researched as an alternative strategy. Statins, which are known for their cholesterol-lowering effects, are considered potential interventions for NAFLD. This review aimed to present the current understanding of the effects of statins on liver physiology in the context of NAFLD. The pathophysiology of NAFLD includes steatosis, inflammation, and fibrosis, which are exacerbated by dyslipidemia and insulin resistance. Statins, which inhibit 3-hydroxy-3-methylglutaryl-CoA reductase, have pleiotropic effects beyond cholesterol-lowering and affect pathways related to inflammation, fibrogenesis, oxidative stress, and microcirculation. Although clinical guidelines support the use of statins for dyslipidemia in patients with NAFLD, more studies are needed to demonstrate their efficacy in liver disease. This comprehensive review serves as a foundation for future studies on the therapeutic potential of statins in NAFLD.

Ovarian cancer (OC) is the most lethal gynecological malignancy and a major global health concern, often diagnosed at advanced stages with poor survival rates. Despite advancements in treatment, resistance to standard chemotherapy remains a critical challenge with limited treatment options available. In recent years, the role of metabolic reprogramming in OC has emerged as a key factor driving tumor progression, therapy resistance, and poor clinical outcomes.

This review explores the intricate connections between metabolic syndrome, enhanced glycolysis, and altered lipid metabolism within OC cells, which fuel the aggressive nature of the disease. We discuss how metabolic pathways are rewired in OC to support uncontrolled cell proliferation, survival under hypoxic conditions, and evasion of cell death mechanisms, positioning metabolic alterations as central to disease progression. The review also highlights the potential of repurposed metabolic-targeting drugs, such as metformin and statins, which have shown promise in preclinical studies for their ability to disrupt these altered metabolic pathways.

Drug repurposing offers a promising strategy to overcome chemoresistance and improve patient outcomes. Future research should focus on unraveling the complex metabolic networks in OC to develop innovative, targeted therapies that can enhance treatment efficacy and patient survival.

Wound healing is a complex physiological process, with scarring and infection caused by Staphylococcus aureus and Pseudomonas aeruginosa being the most common complications. The reutilization of known medications has received increased attention for their role in cell function as small molecules. Examples of these include lovastatin, a cholesterol-lowering agent, and resveratrol, which have multiple biological properties. Both molecules have been reported to improve wound healing and possess antibacterial properties, with conflicting results. The wound-healing capabilities of human mesenchymal stem cells were evaluated after exposure to lovastatin, resveratrol, and their combination through scratch test, migrations assay, and qPCR. Protein docking was performed to assess the lovastatin/resveratrol combination as potential wound-healing targets. AlamarBlue assay was used to determine cell viability. Additionally, the impact of lovastatin and resveratrol combination to inhibit the growth of S. aureus and P. aeruginosa was tested using broth microdilution test and checkerboard assay to determine synergism. The combination of lovastatin 0.1 μM and resveratrol 0.1 μM synergistically improved wound healing and demonstrated an additive effect against S. aureus and P. aeruginosa, presenting potential antibacterial applications.

Statins are widely used for treating lipid disorders and cardiovascular diseases. However, the therapeutic efficiency and adverse effects of statins vary among different patients, which numerous clinical and epidemiological studies have attributed to genetic polymorphisms in statin-metabolizing enzymes and transport proteins. The metabolic processes of statins are relatively complex, involving spontaneous or enzyme-catalyzed interconversion between more toxic lactone metabolites and active acid forms in the liver and bloodstream, influenced by multiple factors, including the expression levels of many metabolic enzymes and transporters. Addressing the variable statin therapeutic outcomes is a pressing clinical challenge. Transcription factors and epigenetic modifications regulate the metabolic enzymes and transporters involved in statin metabolism and disposition and, therefore, hold promise as 'personalized' targets for achieving optimized statin therapy. In this review, we explore the potential for customizing therapy by targeting the metabolism of statin medications. The biochemical bases of adverse reactions to statin drugs and their correlation with polymorphisms in metabolic enzymes and transporters are summarized. Next, we mainly focus on the regulatory roles of transcription factors and epigenetic modifications in regulating the gene expression of statin biochemical machinery. The recommendations for future therapies are finally proposed by targeting the central regulatory factors of statin metabolism.

The gold standard in the non-surgical treatment of periodontitis is scaling and root planning (SRP). In recent years, studies have emerged suggesting additional clinical benefits from the use of statins as an adjunct to classical periodontal disease treatment. The aim of the present study was to review the relevant literature relating to the subgingival use of statins as an adjunctive treatment to the classical, non-surgical treatment of periodontitis, with a particular focus on groups with general factors that may affect the outcome of treatment.

The authors conducted a systematic review following the PRISMA 2020 guidelines. The electronic literature search conducted included the MEDLINE (PubMed) database, Web of Science, Scopus, and Google Scholar from 1 January 2012 to 14 June 2024. The keywords used for the PubMed search were determined with the help of the MeSH Browser Tool and were as follows: Periodontitis [Mesh] AND Statin [Mesh] OR Simvastatin [Mesh] OR Atorvastatin [Mesh] or Rosuvastatin Calcium [Mesh]. Based on the authors' inclusion and exclusion criteria, 20 results were included in the review, out of 937.

The improvement was more pronounced in patients without systematic diseases compared to those with type II diabetes and in non-smokers compared to smoking patients. Greater improvements in clinical and radiological parameters were seen in patients diagnosed with aggressive periodontitis compared to patients with chronic periodontitis.

This literature review led the authors to the conclusion that statins applied locally might be competent agents for improving the therapeutic outcomes of SRP.

In the past decade, a variety of immune checkpoint inhibitors (ICIs) are currently approved for lung cancer in the world. As a new therapeutic approach, ICIs have shown significant clinical benefits in the first-line or second-line treatment for advanced lung cancer, improving the survival and quality of life of patients. Patients need to take multiple drugs in the meantime due to their own disease or side effects during treatment. In view of drug interactions, concomitant medications have a positive or negative impact on the prognosis of lung cancer patients. In this review, we reviewed the effects of multiple drugs on the prognosis of patients with lung cancer taking ICIs. Several studies indicate that antibiotics, proton pump inhibitors (PPIs), corticosteroids, and opioid analgesics can decrease the efficacy of ICIs. Aspirin and bone-targeting drugs can enhance the efficacy of ICIs and improve the survival rate. The effects of metformin (MET), renin-angiotensin-aldosterone system inhibitors (RASI), nonsteroidal anti-inflammatory drug (NSAIDS) (except aspirin), and statins on ICIs are controversial. Future research should further explore the effects of these concomitant medications on ICIs and develop personalized prescriptions based on the specific needs of patients.

Statins, as an important class of lipid-lowering drugs, play a key role in the prevention and treatment of cardiovascular diseases. However, with their widespread use in clinical practice, some adverse events have gradually emerged. In particular, the hepatotoxicity associated with statins use has become one of the clinical concerns that require sufficient attention.

In this study, we conducted a comprehensive and detailed analysis of the hepatotoxicity of statins based on the data of the US Food and Drug Administration Adverse Event Reporting System database from the first quarter (Q1) of 2004 to the Q1 of 2024 and used Reporting Odds Ratios and Empirical Bayes Geometric Mean to mine the signal of adverse events.

In this study, hepatic disorder related seven statins all exhibited positive signals. Through signal mining, we identified a total of 14,511 cases of adverse events associated with hepatic disorder caused by these statin drugs, with atorvastatin, simvastatin, and rosuvastatin occurring at a higher rate. A total of 148 positive signals related to adverse events of hepatic disorder were captured. Autoimmune hepatitis and drug-induced liver injury both presented positive signals across multiple statin drugs. Notably, atorvastatin had the most significant signal strength in cholestatic pruritus and bilirubin conjugation abnormal. Fluvastatin also showed notable signal strength in autoimmune hepatitis, while simvastatin had a relatively weaker signal strength for hepatic enzyme increased.

This study discovered specific adverse event signal values, revealing potential hepatotoxic risks associated with the use of statin drugs. The results provide an important reference for the safe clinical use of drugs, help to improve the understanding of the safety of statins, and also provide a scientific basis for clinicians to make more accurate and safe decisions when making treatment plans.

To investigate the effects of simvastatin as an antimicrobial, considering its influence on the mevalonate pathway and the bacterial cell wall of S. aureus.

S. aureus ATCC 29213 and 33591 were exposed to simvastatin in the presence of exogenous mevalonate to determine whether mevalonate could reverse the inhibition. S. aureus was also treated with simvastatin and gene expression analysis assays were performed to evaluate genes associated with the mevalonate pathway (mvaA, mvaS, mvaK1, and mvaK2), peptidoglycan synthesis (uppS, uppP, and murG), and cell wall stress (vraX, sgtB, and tcaA). Transmission electron microscopy was used to identify the presence of morphological changes. The data were compared using two-way ANOVA and Bonferroni post-test, or the Mann-Whitney test. Addition of exogenous mevalonate was able to partially or completely reverse the inhibition caused by simvastatin. A significant increase of the vraX gene and a reduction of the mvaA gene were observed, together with changes in bacterial morphology.

Simvastatin can exert its antimicrobial effect by means of changes in the cell wall associated with the mevalonate pathway.

The repurposing of statins as neuroprotective agents and/or anti-brain tumor drugs is limited by challenges in brain bioavailability and systemic off-target effects. Therefore, improved and targeted delivery of statins to the brain is necessary. This study aimed to develop a high-strength liquid formulation of the poorly soluble prodrug simvastatin for intranasal administration, as a strategy to achieve high brain concentrations of the prodrug and/or its active form, tenivastatin. Cationic simvastatin nanoemulsions (c-NE) and self-microemulsifying drug delivery systems (c-SMEDDS) were screened for composition, extensively characterized, and the viscosity of the nanoemulsion was further optimized. The optimized c-NE and c-SMEDDS formulations achieved high drug strengths, approximately 5.5% and 9% (w/w), respectively. They formed highly homogeneous aqueous dispersions (polydispersity index < 0.1) with small droplet sizes (< 120 nm and ~ 25 nm, respectively) and remained stable for at least four months under refrigeration. Neither the c-NE nor the c-SMEDDS induced hemolysis up to concentrations of 40 µg/mL and 450 µg/mL of simvastatin, respectively. The zero-shear viscosity of the c-NE was increased to 186 mPa·s by incorporating 0.25% (w/w) polyvinylpyrrolidone, which approached the viscosity of the c-SMEDDS (~ 126 mPa·s). Following intranasal administration of the optimized formulations to Wistar rats at a dose of 10 mg/kg, simvastatin levels in the brain reached 50 to 150 ng/g between 15 and 60 min post-administration. These findings indicate that the developed c-NE and c-SMEDDS formulations hold promise for simvastatin intranasal delivery and brain targeting, potentially paving the way for the realization of simvastatin's neuroprotective potential.

Pulmonary function tests offer crucial parameters for evaluating lung health and predicting clinical outcomes. Hyperlipidemia, a prevalent metabolic disorder, has been linked to declining pulmonary function. Statins are an essential therapy for lowering lipid levels in hyperlipidemia.

This study aims to investigate the therapeutic potential of statins in mitigating the decline in pulmonary function.

This is a retrospective cohort study.

Out of 8286 patients who underwent spirometry testing from January 2018 to December 2020, 492 patients were included in the final analysis. The relationship between statin usage, dosage, along with other biometric indices and spirometry parameters were evaluated. Multivariate logistic regression analyses were employed to assess the association between statin use and the decline in pulmonary function.

In patients with persistent hyperlipidemia, the use of statins was associated with a higher predicted percentage of forced expiratory volume in 1 second (FEV1) compared to non-users (84.0% vs 78.0%, p = 0.015). Logistic regression models further revealed that statin use independently prevented FEV1 decline, irrespective of dosage (adjusted OR 0.036, 95% CI: 0.002-0.618 in lower statins dose group and adjusted OR 0.170, 95% CI: 0.019-1.552 in higher statins dose group).

The findings suggested that statin usage, regardless of dosage, independently mitigated the decline in pulmonary function among patients with persistent hyperlipidemia. Early initiation of statin therapy may hold promise for individuals experiencing hyperlipidemia and declining pulmonary function.

The purpose of this study is to investigate the reporting of risks associated with transporter-mediated drug-drug interactions (DDIs) in medicinal product information and to identify suitable wording for future standardisation of summaries of product characteristics (SmPCs).

The SmPCs of medicinal products approved in the European Union from 2012 to 2023 were screened for warnings on Organic Anion Transporting Polypeptide 1B1 and 1B3 (OATP1B1 and OATP1B3), and Breast Cancer Resistance Protein (BCRP). An in-house search engine for product information was used. Warnings were categorised into different DDI scenarios based on the SmPC texts.

A total of 192 out of 859 approved medicinal products had SmPC text pertaining to OATP1B1, 1B3 and/or BCRP. The majority of products had text for all three transporters Most texts were located in SmPC Sect. 5.2, followed by Sect. 4.5. Numerous interaction-texts either concluded that the interaction lacked clinical relevance or lacked information on the clinical relevance of the finding. The highest number of SmPC texts indicating a clinically relevant interaction with outlined clinical consequences was found for BCRP. The article also presents SmPC texts for each DDI scenario, which the authors consider as examples of explicit wordings with actionable recommendations.

A potential for improvement of SmPC text for transporter-mediated DDI was identified: Warnings without clinical relevance could be omitted, and some warnings with clinical relevance could be updated to provide actionable recommendations to the prescribers. A selection of unambiguous texts was identified as starting point to generate standard texts.

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a spectrum of liver lesions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH), that may further progress to cirrhosis. MASLD is estimated to affect more than one third of the general population and it represents a risk factor for end-stage liver failure and liver cancer, substantially contributing to liver-related morbidity and mortality. Although the pathogenesis of MASLD is incompletely understood, it is known to consist of a multifactorial process influenced by extrinsic and intrinsic factors such as metabolic, environmental and demographic features, gut microbiota and genetics. Dysregulation of both extracellular and intracellular lipid composition is known to promote the generation of toxic lipid species, thereby triggering lipotoxicity and cellular stress. These events ultimately lead to the activation of distinct cell death pathways, resulting in inflammation, fibrogenesis and, eventually, carcinogenesis. In this manuscript, we provide a comprehensive review of the role of lipotoxicity during MASLD pathogenesis, discussing the most relevant lipid species and related molecular mechanisms, summarizing the cell type-specific effects and highlighting the most promising putative therapeutic strategies for modulating lipotoxicity and lipid metabolism in MASLD.

Atorvastatin (ATOR) acts on certain antitumor pathways; the consequences of chemotherapies continue to be a major concern, notwithstanding the increased efficacy provided by contemporary therapies. This study investigated the synergistic effects and underlying mechanisms of different treatment protocols using ATOR on the THP-1 cell line and on lung cancer in mice. For the in vitro study, an MTT assay was performed, and then different combinations against the THP-1 cell line were used as follows: non-treated cells, THP-1/ATOR IC50, THP-1/cytarabine (CYT) IC50, THP-1/doxorubicin (DOX) IC50, THP-1/DOX/CYT, THP-1/ATOR/CYT, THP-1/ATOR/DOX, and THP-1/ATOR/CYT/DOX. For the in vivo study, CD-1 male mice were used; G1 was the normal control. Gs2-5 were administered with urethane (Ure) and butylated hydroxytoluene (BHT). G2 was the positive control. G3 was treated with ATOR (20 mg/kg). G4 was treated with Bevacizumab (Bev) (5 mg/kg). G5 was co-treated with ATOR/Bev. Histopathological and immunohistochemical investigations, flow cytometry and molecular analysis of PI3K, Akt, and mTOR genes were performed after different treatment protocols. The results showed that different combinatorial treatment settings of ATOR in vitro increase the apoptotic-inducing capacity and cell cycle arrest. Co-treatment with ATOR and Bev led to a significant decrease in S-phase and G2/M percentages. Furthermore, in vivo co-treatment with ATOR/Bev decreased tumor incidence and size with a significant reduction of the immunohistochemical PCNA (LI%) in lung parenchyma, targeting PI3K/Akt/mTOR, and VEGF-A signaling pathways. Co-treatment with ATOR and chemotherapies led to cell cycle arrest, modulation of the PI3K/Akt/mTOR, and VEGF-A signaling pathways in tumor cells.

The objective of this study was to examine the hypolipidemic effect and potential mechanism of action of green radish polysaccharide (GRP) in hyperlipidemic mice. We found that in mice fed a high-fat diet, supplementing with GRP reduced body weight and liver index, significantly improved serum lipid levels and markers of liver damage, and mitigated oxidative stress and inflammation. Mechanistically, in these hyperlipidemic mice, the size of fat cells was reduced by GRP, and the abnormal accumulation of lipid droplets was reduced. We also found that GRP regulates the composition of the intestinal microbiota, including the ratio of Firmicutes to Mycobacteria F/B and the levels of Blautia spp., which have been shown to alleviate liver damage and treat hyperlipidemia. Metabolite pathway analysis using the Kyoto Encyclopedia of Genes and Genomes identified the glycolysis/glycolytic metabolism and propionate metabolism pathways as potential targets for GRP in the amelioration of hyperlipidemia.

HMG-CoA reductase inhibitors are well-known medications in the treatment of cardiovascular disorders due to their pleiotropic and lipid-lowering properties. Herein, we reviewed the effects of statins on the CCL2/CCR2 axis.

Scopus and Pubmed databases were systematically searched using the following keywords:" Hydroxymethylglutaryl CoA Reductase Inhibitors"," HMG-CoA Reductase Inhibitors"," Statins", "CCL2, Chemokine", "Monocyte Chemoattractant Protein-1" and "Chemokine (C-C Motif) Ligand 2". Evidence investigating the role of statin on MCP-1 in CVD was identified and bibliographies were completely evaluated to gather further related studies.

The anti-inflammatory effects of statins on the CCL2/CCR2 pathway have been widely investigated. Despite inconclusive results, a great body of research supports the regulatory roles of statins on this pathway due to their pleiotropic effects. By disrupting the CCL2/CCR2 axis, statins attenuate the infiltration of monocytes and macrophages into the zone of inflammation and hence down-regulate the inflammatory cascades in various CVDs including atherosclerosis, cardiac remodeling, and stroke, among others.

CCL2 plays a major role in the pathogenesis of cardiovascular disorders. Down-regulation of CCL2 is proposed as one of the pleiotropic properties of statins. However, more investigations are required to elucidate which statin in what dose exerts a more potent effect on CCL2/CCR2 pathway.