• Blood concentration
• Hydroxychloroquine
• Mechanisms of action
• Research progress
• Systemic lupus erythematosus

Cardiovascular diseases (CVD) are one of the leading causes of high mortality in patients with systemic lupus erythematosus (SLE). The Framingham risk score and other traditional risk factors do not fully reflect the CVD risk in SLE patients. Therefore, in order to stratify these high-risk patients, additional biomarkers for subclinical CVD are needed. The mechanisms of atherogenesis in SLE are still being investigated. During the past decades, many reports recognized that inflammation plays a crucial role in the development of atherosclerosis. The aim of this report is to present novel proinflammatory and pro-atherosclerotic risk factors that are closely related to SLE inflammation and which determine an increased risk for the occurrence of early cardiovascular events.

• Humans
• Atherosclerosis/etiology
• Atherosclerosis/epidemiology
• Lupus Erythematosus, Systemic/complications
• Risk Factors
• Cardiovascular Diseases/epidemiology
• Inflammation/complications
• Biomarkers

Patients with systemic lupus erythematosus (SLE) are at increased risk of cardiovascular disease (CVD) compared to the general population. However, little is known about the effects of tobacco smoking on CVD in patients with SLE.

To systematically review and summarize the available literature regarding the effects of tobacco smoking on developing CVD in patients with SLE.

We retrieved relevant studies from the following databases: PubMed, EMBASE, Web of Science and China National Knowledge Internet (CNKI) database. Two reviewers independently reviewed the eligible studies, assessed their validity, and extracted relevant data. Sensitivity and subgroup analyses were performed to distinguish sources of heterogeneity.

A total of 10 studies, which comprised 6984 participants, were included in the analysis. The overall quality of evidence was rated as moderate to low. The smoking prevalence among CVD patients was 39.28% (271/690), which was higher than 31.36% (1974/6294) among non-CVD patients. Compared with never-smokers, the risk of developing CVD in current smokers was 1.42 (95% CI: 1.21–1.66). No significant publication bias was found in our meta-analysis.

In spite of the several negative results, this study found that current smokers with SLE have an increased risk of developing CVD, although most of the included studies were in low-to-moderate quality.

https://www.crd.york.ac.uk/prospero/, identifier CRD42022338109.

• Cardiovascular Diseases/complications
• Cardiovascular Diseases/etiology
• Humans
• Lupus Erythematosus, Systemic/complications
• Lupus Erythematosus, Systemic/epidemiology
• Prevalence
• Smoking/adverse effects
• Smoking/epidemiology
• Tobacco Smoking/adverse effects
• Tobacco Smoking/epidemiology

• National Natural Science Foundation of China

This review describes the complex interplay between inflammation, vasculopathy and fibrosis that involve the heart and peripheral small vessels, leading to endothelial stiffness, vascular damage, and early aging in patients with systemic lupus erythematosus and systemic sclerosis, which represents two different models of vascular dysfunction among systemic autoimmune diseases. In fact, despite the fact that diagnostic methods and therapies have been significantly improved in the last years, affected patients show an excess of cardiovascular mortality if compared with the general population. In addition, we provide a complete overview on the new techniques which are used for the evaluation of endothelial dysfunction in a preclinical phase, which could represent a new approach in the assessment of cardiovascular risk in these patients.

• Disease severity
• IgA vasculitis nephritis
• Transthyretin

• Capillaroscopy
• case-control
• childhoodonset
• pediatric
• systemic lupus erythematosus

• Endothelial dysfunction
• SLE
• T lymphocytes
• angiogenic T cells
• microvascular
• regulatory T cells.

Lupus nephritis (LN) is one of the most common and severe complications of lupus. However, the mechanisms for renal damage have not been well elucidated. There are evidences show that glomerular endothelial cells (GECs) are damaged in LN. Immune complexes can deposit in subendothelial area and could affect GEC functions. In the present study, we used heat-aggregated gamma globulin (HAGG) to simulate immune complexes and investigated their effects on GEC functions. Our results revealed that HAGG impaired different aspect of the GEC functions. HAGG changed cell morphology, upregulated the expression of active caspase-3, inhibited angiogenesis, and increased NO production in GECs. These results provide new clues for the mechanisms of renal damage and the pathology of LN.

• glomerular endothelial cells functions
• immune complexes
• lupus nephritis

• Caspase 3/metabolism
• Cells, Cultured
• Endothelial Cells/cytology
• Endothelial Cells/drug effects
• Endothelial Cells/metabolism
• Hot Temperature
• Humans
• Kidney Glomerulus/cytology
• Lupus Nephritis/metabolism
• Lupus Nephritis/pathology
• Necrosis
• Neovascularization, Physiologic/drug effects
• Nitric Oxide/metabolism
• Tumor Necrosis Factor-alpha/pharmacology
• Up-Regulation/drug effects
• gamma-Globulins/immunology
• gamma-Globulins/pharmacology

• CVR
• Ps
• PsA
• Pulse wave velocity
• eEPCs

Endothelium-dependent flow-mediated dilation (ED-FMD), a biophysical marker of endothelial dysfunction, is apparently impaired in patients with systemic lupus erythematosus (SLE) but such observation is inconsistent. Here, we assessed and compared the brachial artery ED-FMD (baED-FMD) using ultrasonography between SLE patients without cardiovascular disease and healthy controls (HC) matched for age, gender and body mass index. We then performed a comprehensive meta-analysis of case-control studies which compared baED-FMD between SLE patients and HC by determining the effect size of baED-FMD as standardized mean difference (SMD). Factors associated with the effect size were explored by mixed-model meta-regression. Seventy one SLE patients and 71 HC were studied. SLE patients had lower baED-FMD than HC (3.72 ± 2.8% vs 4.63 ± 3.1%, p = 0.032). Meta-analysis of 25 case-control studies involving 1,313 SLE patients and 1,012 HC with the random effects model revealed lower baED-FMD in SLE patients compared to HC (SMD −1.077, p < 0.001). The presence of diabetes mellitus (p = 0.04747), higher diastolic blood pressure (p = 0.044), renal involvement (p = 0.027) and aspirin use (p = 0.001) were associated with more discrepant baED-FMD between both groups. In conclusion, SLE patients naïve of cardiovascular disease have impaired endothelial function. Diabetes mellitus, renal disease and diastolic hypertension are major contributors of endothelial dysfunction in SLE patients.

• bronchial asthma
• laser Doppler flowmetry
• lung obstruction
• microcirculation
• postocclusive reactive hyperemia
• skin blood flow oscillations
• time-amplitude analysis

• Cytokines
• Fli-1
• G-CSF
• Gene regulation
• Inflammation
• Transcriptional factors

• dialysis
• disease recurrence
• end-stage kidney disease
• kidney transplantation
• outcomes
• renal transplantation
• systemic lupus erythematosus

Air pollution is a major challenge to public health. Ambient fine particulate matter (PM) is the key component for air pollution, and associated with significant mortality. The majority of the mortality following PM exposure is related to cardiovascular diseases. However, the mechanisms for the adverse effects of PM exposure on cardiovascular system remain largely unknown and under active investigation. Endothelial dysfunction or injury is considered one of the major factors that contribute to the development of cardiovascular diseases such as atherosclerosis and coronary heart disease. Endothelial progenitor cells (EPCs) play a critical role in maintaining the structural and functional integrity of vasculature. Particulate matter exposure significantly suppressed the number and function of EPCs in animals and humans. However, the mechanisms for the detrimental effects of PM on EPCs remain to be fully defined. One of the important mechanisms might be related to increased level of reactive oxygen species (ROS) and inflammation. Bone marrow (BM) is a major source of EPCs. Thus, the number and function of EPCs could be intimately associated with the population and functional status of stem cells (SCs) in the BM. Bone marrow stem cells and other SCs have the potential for cardiovascular regeneration and repair. The present review is focused on summarizing the detrimental effects of PM exposure on EPCs and SCs, and potential mechanisms including ROS formation as well as clinical implications.

• PM
• air pollution
• cardiovascular disease
• endothelial progenitor cell
• stem cell

• Biomarkers/blood
• Cytokines/blood
• Dietary Supplements
• Drugs, Chinese Herbal/pharmacology
• Drugs, Chinese Herbal/therapeutic use
• Endothelium, Vascular/cytology
• Endothelium, Vascular/drug effects
• Endothelium, Vascular/metabolism
• Enzyme-Linked Immunosorbent Assay
• Flow Cytometry
• Humans
• Interleukin-18/blood
• Lupus Erythematosus, Systemic/drug therapy
• Lupus Erythematosus, Systemic/metabolism
• Medicine, Chinese Traditional
• Placebo Effect
• Vascular Endothelial Growth Factor A/blood

Thrombotic events, both arterial and venous, are a major health concern worldwide. Further, autoimmune diseases, such as systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, and antiphospholipid syndrome, predispose to thrombosis, and thereby push the risk for these morbid events even higher. In recent years, neutrophils have been identified as important players in both arterial and venous thrombosis. Specifically, chromatin-based structures called neutrophil extracellular traps (NETs) play a key role in activating the coagulation cascade, recruiting platelets, and serving as scaffolding upon which the thrombus can be assembled. At the same time, neutrophils and NETs are emerging as important mediators of pathogenic inflammation in the aforementioned autoimmune diseases. Here, we first review the general role of NETs in thrombosis. We then posit that exaggerated NET release contributes to the prothrombotic diatheses of systemic lupus erythematosus, ANCA-associated vasculitis, and antiphospholipid syndrome.

• Thrombosis
• Neutrophil extracellular traps
• Lupus
• Vasculitis
• Antiphospholipid syndrome

• K08 AR066569 NIAMS NIH HHS

• CVD
• SLE
• immune mechanisms
• immunotherapy

Systemic lupus erythematosus (SLE) is a heterogeneous multifactorial systemic autoimmune disease affecting several organs. SLE can start relatively early in life and results in impaired quality of life and shortened life expectancy because of a gradual disease progression leading to cardiovascular, renal and neoplastic disease. The basic mechanisms of the pathogenesis of the disease still remain to be clarified. It is clear that complement proteins play a key and complex role in the development of SLE. Complement component C1q has been known to be a fundamental component of lupus development, but most explanations focus on its role in apoptotic debris removal. Importantly, C1q was recently found to play a key role in the maintenance of vascular endothelial integrity.

We suggest that apoptotic products, endothelial cells and extracellular matrix components, which display negatively charged moieties, compete for binding to molecules of the innate humoral immune response, like C1q. Genetic or acquired factors leading to an increased load of apoptotic cell debris and decrease or absence of C1q therefore interfere with the regulation of endothelial permeability and integrity. Furthermore, we suggest that lupus is the net result of an imbalance between the two functions of immune clearance and vascular endothelial integrity maintenance, an imbalance triggered and sustained by autoimmunity, which skews C1q consumption by IgG-mediated complement classical pathway activation on autoantigens. In this triangle of innate clearance, autoimmunity and endothelial integrity, C1q plays a central role.

Hence, we interpret the pathogenesis of lupus by identifying three key components, namely innate immune clearance, autoimmunity and endothelial integrity and we establish a link between these components based on the protective role that innate clearance molecules play in endothelial renewal. By including the vasoprotective role of C1q in the interpretation of SLE development we attempt to provide novel explanations for the symptoms, organ damage, diagnostic and therapeutic difficulties of the disease.

• C1q
• IgM
• SLE
• apoptosis
• autoantibody
• autoimmunity
• clearance
• complement
• endothelium
• lupus
• natural
• pathogenesis
• systemic lupus erythematosus

Although cigarette smoke is known to be a complex mixture of over 4000 substances that can lead to damage through active or passive smoking, its mechanisms and biochemical consequences in pregnancy and neonates are not yet fully understood. Therefore, in the present study, we propose to study the impact of smoking during gestation on the viability of blood mononuclear cells (MNC) from umbilical cords of newborns to assess the degree of oxidative stress and cell viability. After childbirth, the cord blood and the umbilical cord were immediately collected in public hospitals in Greater Vitoria, ES, Brazil. Flow cytometry was used to analyze the cord blood followed by biochemical and histological tests to analyze possible changes in the umbilical cord.

Pregnant smokers had a reduction of MNC viability from the umbilical cord (10%), an increase in the production of reactive oxygen species (ROS) and an increase in cell apoptosis (~2-fold) compared to pregnant non-smokers. In the umbilical cord, it was observed an increase of advanced oxidation protein products - AOPP (~2.5-fold) and a loss of the typical architecture and disposition of endothelial cells from the umbilical artery.

These data suggest that maternal cigarette smoking during pregnancy (even in small amounts) may compromise the viability of MNC cells and damage the umbilical cord structure, possibly by excessive ROS bioavailability.