• Iso@PEG‐GK
• SH2 domain
• STAT3
• diabetic nephropathy
• dimerization
• isoquercitrin
• phosphorylation

• 2022YFC3602000 National Key Research and Development Program of China
• 32141005 National Natural Science Foundation of China
• 82274327 National Natural Science Foundation of China

• Ischemia/reperfusion injury
• Ischemic preconditioning
• MicroRNAs

• MicroRNAs/genetics
• MicroRNAs/metabolism
• Humans
• Reperfusion Injury/metabolism
• Reperfusion Injury/pathology
• Reperfusion Injury/genetics
• Ischemic Preconditioning
• Animals
• Oxidative Stress

• 4020122 Yasuj University of Medical Sciences

• Aerobic exercise
• Cardiovascular risk
• Circulating endothelial (progenitor) cell
• Flow mediated dilation
• Sedentary
• Static retinal vessel analysis
• microRNA

• Humans
• Male
• Endothelium, Vascular/physiopathology
• Female
• Middle Aged
• Cardiovascular Diseases/physiopathology
• Cardiovascular Diseases/prevention & control
• Adult
• Heart Disease Risk Factors
• Exercise
• MicroRNAs/metabolism
• MicroRNAs/blood
• Vasodilation
• Brachial Artery
• Sedentary Behavior
• Exercise Therapy/methods
• Retinal Vessels
• Time Factors
• Treatment Outcome
• Epigenesis, Genetic

• Acute kidney injury
• Cardiac arrest
• Cardio pulmonary resuscitation
• Influencing factors
• Nomogram

• Humans
• Acute Kidney Injury/therapy
• Acute Kidney Injury/diagnosis
• Acute Kidney Injury/etiology
• Retrospective Studies
• Cardiopulmonary Resuscitation/adverse effects
• Male
• Female
• Heart Arrest/therapy
• Heart Arrest/diagnosis
• Heart Arrest/physiopathology
• Risk Assessment
• Middle Aged
• Aged
• Predictive Value of Tests
• Risk Factors
• Treatment Outcome
• Biomarkers/blood
• Reproducibility of Results
• Databases, Factual
• Decision Support Techniques

• blood‐derived endothelial cell
• cardiovascular
• chronic kidney disease
• indoxyl sulfate
• microfluidics
• organs‐on‐chip
• uremic toxin

• Humans
• Microvessels/pathology
• Cardiovascular Diseases
• Animals
• Swine
• Renal Insufficiency/therapy
• Risk Assessment
• Tissue Donors
• Tissue Engineering/methods
• Indican/blood

• Lymphatic Malformation Institute
• 2021-FLG-3814 North Carolina Biotechnology Center
• 857738 American Heart Association-American Stroke Association
• F31HL162462 NHLBI NIH HHS
• T32DK007750 NIDDK NIH HHS
• North Carolina Research Triangle Nanotechnology Network
• National Science Foundation
• National Nanotechnology Coordinated Infrastructure
• T32 DK007750 NIDDK NIH HHS
• CLOVES Syndrome Community
• T32HL69768 National Institutes of Health through the Integrative Vascular Biology Training Program
• R01 DK132328 NIDDK NIH HHS
• T32 HL069768 NHLBI NIH HHS
• R35 GM142944-01 NIGMS NIH HHS
• CDA857738 American Heart Association
• R35 GM142944 NIGMS NIH HHS
• F31 HL162462 NHLBI NIH HHS

We created a comprehensive reference atlas of normal human kidney endothelial cells. We confirmed that endothelial cell types in the human kidney were also highly conserved in the mouse kidney.

Kidney endothelial cells are exposed to different microenvironmental conditions that support specific physiologic processes. However, the heterogeneity of human kidney endothelial cells has not yet been systematically described.

We reprocessed and integrated seven human kidney control single-cell/single-nucleus RNA sequencing datasets of >200,000 kidney cells in the same process.

We identified five major cell types, 29,992 of which were endothelial cells. Endothelial cell reclustering identified seven subgroups that differed in molecular characteristics and physiologic functions. Mapping new data to a normal kidney endothelial cell atlas allows rapid data annotation and analysis. We confirmed that endothelial cell types in the human kidney were also highly conserved in the mouse kidney and identified endothelial marker genes that were conserved in humans and mice, as well as differentially expressed genes between corresponding subpopulations. Furthermore, combined analysis of single-cell transcriptome data with public genome-wide association study data showed a significant enrichment of endothelial cells, especially arterial endothelial cells, in BP heritability. Finally, we identified M1 and M12 from coexpression networks in endothelial cells that may be deeply involved in BP regulation.

We created a comprehensive reference atlas of normal human kidney endothelial cells that provides the molecular foundation for understanding how the identity and function of kidney endothelial cells are altered in disease, aging, and between species. Finally, we provide a publicly accessible online tool to explore the datasets described in this work (https://vascularmap.jiangnan.edu.cn ).

• bp
• cardiovascular
• endothelial cells
• kidney

• Humans
• Endothelial Cells/metabolism
• Single-Cell Analysis
• Transcriptome
• Kidney/cytology
• Gene Expression Profiling

• 82070508 National Natural Science Foundation of China
• 91939301 National Natural Science Foundation of China
• 81622007 National Natural Science Foundation of China
• 81870362 National Natural Science Foundation of China
• 82025005 National Natural Science Foundation of China
• Q2015106 the Chang Jiang Scholars Program
• 82100416 National Natural Science Foundation of China

• acute kidney injury
• nanomaterials
• oxidative stress
• reactive oxygen species
• renal targeting

• National Natural Science Foundation of China

• cell adhesion molecules
• glycocalyx
• hyaluronan
• lupus nephritis
• syndecan-1
• thrombomodulin

• Humans
• Lupus Nephritis/pathology
• Glycocalyx/pathology
• Kidney/pathology
• Biomarkers
• Endothelial Cells/pathology

• cardiovascular disease
• endothelial dysfunction
• extracellular vesicles
• ferric carboxymaltose
• heart failure
• iron
• microparticles
• microvesicles

• Ultrasound
• endothelium
• fibrosis
• inflammation
• kidney
• predictive

• Humans
• Endothelium, Vascular/diagnostic imaging
• ROC Curve
• Acute Kidney Injury/diagnostic imaging
• Biomarkers
• Ultrasonography
• Sepsis

• cardiovascular disease
• diabetes
• host immune response
• periodontal disease
• selectin
• systemic disease
• therapeutic target

• Humans
• Quality of Life
• Endothelial Cells
• Selectins
• Periodontal Diseases/therapy
• Immunotherapy
• Periodontitis/therapy
• Immunologic Factors
• Vascular Diseases

• Vote Number: STG-000108 Jeffrey Cheah School of Medicine and Health Sciences Strategic Grant 2022
• RMF1252-2021 University of Malaya Research Grant

• Chronical kidney disease
• Endothelial injury
• Hyperuricemic nephropathy
• Inflammation
• Risk factors

• Acute exercise
• Circulating endothelial (progenitor) cell
• Endothelial dysfunction

Early vascular aging (EVA) is increasingly prevalent in the general population. Exercise is important for primary cardiovascular prevention, but often insufficient due to ineffective training methods and a lack of biomarkers suitable to monitor its vascular effects. VascuFit will assess the effectiveness of non-linear periodized aerobic exercise (NLPE) in a non-athletic sedentary population to improve both established and promising biomarkers of EVA.

Forty-three sedentary adults, aged 40–60 years, with elevated cardiovascular risk will either engage in 8 weeks of ergometer-based NLPE (n = 28) or receive standard exercise recommendations (n = 15). The primary outcome will be the change of brachial-arterial flow-mediated dilation (baFMD) after versus before the intervention. Secondary outcomes will be the change in static vessel analysis (SVA; clinical biomarker of microvascular endothelial function), endomiRs (microRNAs regulating key molecular pathways of endothelial cell homeostasis) and circulating cellular markers of endothelial function (mature endothelial cells, endothelial progenitor cells). Tertiary outcomes will be the change in sphingolipidome, maximum oxygen capacity, and traditional cardiovascular risk factors (blood pressure, triglycerides, cholesterol, fasting glucose, high-sensitivity C-reactive protein).

We expect an improvement of baFMD of at least 2.6% and significant pre-post intervention differences of SVA and endomiRs as well as of the tertiary outcomes in the intervention group. VascuFit may demonstrate the effectiveness of NLPE to improve endothelial function, thus vascular health, in the general sedentary population. Furthermore, this project might demonstrate the potential of selected molecular and cellular biomarkers to monitor endothelial adaptations to aerobic exercise.

The trial was registered on www.clinicaltrials.gov (NCT05235958) in February 11^th 2022.

• Aging
• Atherosclerosis
• Cardiovascular Disease
• Exercise
• Exercise Testing
• Non-linear periodized aerobic exercise
• Peripheral Vascular Disease
• Primary Prevention
• Risk Factors

• endothelial cells
• inflammation
• oyster-derived bioactive dodecapeptide
• protein kinase
• thrombin

• Animals
• Cells, Cultured
• Crassostrea/genetics
• Crassostrea/metabolism
• Endothelium, Vascular/metabolism
• Fibrinolytic Agents
• Human Umbilical Vein Endothelial Cells/metabolism
• Humans
• Peptides/metabolism
• Peptides/pharmacology
• Thrombin/pharmacology
• Thrombosis/drug therapy

Vascular endothelial growth factor antagonism with angiogenesis inhibitors in cancer patients induces a ‘preeclampsia-like’ syndrome including hypertension, proteinuria and elevated endothelin (ET)-1. Cyclo-oxygenase (COX) inhibition with aspirin is known to prevent the onset of preeclampsia in high-risk patients. In the present study, we hypothesised that treatment with aspirin would prevent the development of angiogenesis inhibitor-induced hypertension and kidney damage. Our aims were to compare the effects of low-dose (COX-1 inhibition) and high-dose (dual COX-1 and COX-2 inhibition) aspirin on blood pressure, vascular function, oxidative stress, ET-1 and prostanoid levels and kidney damage during angiogenesis-inhibitor therapy in rodents. To this end, Wistar Kyoto rats were treated with vehicle, angiogenesis inhibitor (sunitinib) alone or in combination with low- or high-dose aspirin for 8 days (n=5–7/group). Our results demonstrated that prostacyclin (PGI₂) and ET-1 were increased during angiogenesis-inhibitor therapy, while thromboxane (TXA₂) was unchanged. Both low- and high-dose aspirin blunted angiogenesis inhibitor-induced hypertension and vascular superoxide production to a similar extent, whereas only high-dose aspirin prevented albuminuria. While circulating TXA₂ and prostaglandin F_2α levels were reduced by both low- and high-dose aspirin, circulating and urinary levels PGI₂ were only reduced by high-dose aspirin. Lastly, treatment with aspirin did not significantly affect ET-1 or vascular function. Collectively our findings suggest that prostanoids contribute to the development of angiogenesis inhibitor-induced hypertension and renal damage and that targeting the prostanoid pathway could be an effective strategy to mitigate the unwanted cardiovascular and renal toxicities associated with angiogenesis inhibitors.

• NADPH oxidase
• cyclooxygenase
• endothelins
• hypertension
• vascular endothelial growth factor

• blood
• endothelial cells
• in vitro models
• microfluidics
• organs-on-chips
• permeability
• vasculature

• COVID-19
• Endothelium, Vascular
• Humans
• Microfluidics
• Plasma
• SARS-CoV-2
• Vascular Endothelial Growth Factor A

• COVID-19
• angiogenesis
• endothelial cell dysfunction
• infection
• proteome

• LN
• hyaluronan
• syndecan-1
• thrombomodulin

Smoking can cause vascular damage in the form of an inflammatory reaction characterized by endothelial activation. Endothelial activation forms a pathological adaptation pattern so that it can induce the atherogenesis process. Several markers, such as E-selectin, platelet-derived micro particles (PMPs) and hematopoietic stem cell (HSC) can identify the activation of endothelial in circulating blood. Therefore, the deviation of vascular adaptation due to smoking can be detected early through the feedback mechanism between E-selectin, PMPs, and HSC.

This study aims to analyze the initial picture of the negative impact of smoking on vascular adaptation by measuring E-selectin, PMPs, and HSC in the peripheral blood circulation. Participant criteria and methods: Peripheral blood samples (5 mL) were taken from each participant, both the smoking group (n = 30) and the non-smoker group (n = 31) to obtain peripheral blood mononuclear cells (PBMNC). PBMNC was isolated using ficoll-based gradient centrifugation. The flow cytometry assay method used to measure the E-selectin, PMPs and hematopoietic stem cells.

The mean of circulating E-selectin in smokers was higher than that of non-smokers. On the other hand, the average number of PMPs and HSCs in smokers was lower than non-smokers.

Smoking increases the risk of accelerated vascular block formation, as indicated by an increase in the amount of circulating E-selectin. The increase in E-selectin in the blood vessels mediates the increased adhesion of PMPs in the vascular area so that the number of circulating PMPs in smokers decreases. The decrease in circulating PMPs decreases the signal of vascular repair, which is characterized by a decline in the number of HSCs.

• atherosclerosis
• cardiovascular disease
• endothelial injury
• peripheral blood mononuclear cells
• smoker

• Glycocalyx
• Hematopoietic stem cells
• High-intensity interval training
• Oxygen radical absorbance capacity
• Vascular endothelial cells

Exercise is known to acutely and transiently mobilize precursor cells to the peripheral blood. To date, the underlying mechanisms have not yet been fully elucidated and we hypothesized that exercise-induced oxidative stress could be a mobilizing agent, either directly or via circulating apoptotic cells as mediators. The aim of the study was to assess the effect of acute exercise-induced oxidative stress on numbers of circulating angiogenic precursor cells (CACs), circulating non-angiogenic precursor cells (nCACs), mesenchymal precursor cells (MPCs), mature endothelial cells (ECs), and mononuclear cells (MNCs), as well as their apoptotic subsets. Healthy, young males (n = 18, age: 24.2 ± 3.5 years) completed two identical, standardized incremental cycling tests. The first, un-supplemented control test was followed by a 7-day-long supplementation of vitamin C (1,000 mg/day) and E (400 I.U./day), immediately preceding the second test. Blood samples were collected before, directly after, 30, 90, 180, and 270 min after exercise, and aforementioned circulating cell numbers were determined by flow cytometry and a hematology analyzer. Additionally, total oxidative capacity (TOC) and total antioxidative capacity (TAC) were measured in serum at all timepoints. Antioxidative supplementation abolished the exercise-induced increase in the oxidative stress index (TOC/TAC), and reduced baseline concentrations of TOC and TOC/TAC. However, it did not have any effect on CACs, nCACs, and MPC numbers or the increase in apoptotic MNCs following exercise. Our results indicate that exercise-induced oxidative stress is neither a main driver of lymphocyte and monocyte apoptosis, nor one of the mechanisms involved in the immediate or delayed mobilization of precursor cells.

• acute exhaustive exercise
• apoptosis
• endothelial
• hematopoietic
• mesenchymal
• oxidative stress index
• stem cell mobilization
• total oxidative capacity

Endothelial progenitor cells (EPCs) have been discovered to be relevant to the prognosis of cardiovascular diseases. Previous research has demonstrated that EPCs serve vital roles in the occurrence and development of atherosclerosis. Significant improvements have been made in MRI technology and in the experimental use of EPCs for therapeutic angiogenesis and vascular repair. Nevertheless, the migratory, adhesive, proliferative and angiogenic properties of EPCs remain unknown. The aims of the present study were to investigate the potential of using non-invasive monitoring with ultrasmall superparamagnetic iron oxide nanoparticle (USPION)-labeled endothelial progenitor cells (EPCs) after transplantation, and to assess the treatment outcomes in an atherosclerotic rabbit model. EPCs derived from rabbit peripheral blood samples were labeled with USPION-poly-l-lysine (USPION-PLL). The morphology, proliferation, adhesive ability and labeling efficiency of the EPCs were determined by optical and electron microscopy. Moreover, biological activity was assessed by flow cytometry. In addition, T2-weighted image fast spin-echo MRI was used to detect cell labeling. USPION content in the labeled EPCs was determined by Prussian blue staining and scanning electron microscopy. Rabbit atherosclerosis model was established using a high-fat diet. USPION-labeled EPCs were transplanted into rabbits, and in vivo MRI was performed 1 and 7 days after transplantation. It was found that EPCs cultured on Matrigel formed capillary-like structures, and expressed the surface markers CD133, CD31, CD34 and vascular endothelial growth factor receptor 2 (VEGFR2). The optimal USPION concentration was 32 µg/ml, as determined by adhesion and proliferation assays. It was identified that USPION-PLL nanoparticles were 10–20 nm in diameter. Histopathological analysis results indicated that 1 day after transplantation of the labeled EPCs, blue-stained granules were observed in the intima of vascular lesions in rabbit models after Prussian blue staining. Therefore, the present results suggest that USPION-labeled EPCs may play a role in repairing endothelial injury and preventing atherosclerosis in vivo.

TNFα signaling in the vascular endothelium elicits multiple inflammatory responses that drive vascular destabilization and leakage. Bioactive lipids are main drivers of these processes. In vitro mechanistic studies of bioactive lipids have been largely based on two-dimensional endothelial cell cultures that, due to lack of laminar flow and the growth of the cells on non-compliant stiff substrates, often display a pro-inflammatory phenotype. This complicates the assessment of inflammatory processes. Three-dimensional microvessels-on-a-chip models provide a unique opportunity to generate endothelial microvessels in a more physiological environment. Using an optimized targeted liquid chromatography–tandem mass spectrometry measurements of a panel of pro- and anti-inflammatory bioactive lipids, we measure the profile changes upon administration of TNFα. We demonstrate that bioactive lipid profiles can be readily detected from three-dimensional microvessels-on-a-chip and display a more dynamic, less inflammatory response to TNFα, that resembles more the human situation, compared to classical two-dimensional endothelial cell cultures.

In a range of conditions called autoimmune diseases, the immune system attacks the body rather than foreign elements. This can cause inflammation that is harmful for many organs. In particular, immune cells can produce excessive amounts of a chemical messenger called tumor necrosis factor alpha (TNFα for short), which can lead to the release of fatty molecules that damage blood vessels.

This process is normally studied in blood vessels cells that are grown on a dish, without any blood movement. However, in this rigid 2D environment, the cells become ‘stressed’ and show higher levels of inflammation than in the body. This makes it difficult to assess the exact role that TNFα plays in disease.

A new technology is addressing this issue by enabling scientist to culture blood vessels cells in dishes coated with gelatin. This allows the cells to organize themselves in 3D, creating tiny blood vessels in which fluids can flow. However, it was unclear whether these ‘microvessels-on-a-chip’ were better models to study the role of TNFα compared to cells grown on a plate.

Here, Junaid et al. compared the levels of inflammation in blood vessels cells grown in the two environments, showing that cells are less inflamed when they are cultured in 3D. In addition, when the artificial 3D-blood vessels were exposed to TNFα, they responded more like real blood vessels than the 2D models. Finally, experiments showed that it was possible to monitor the release of fatty molecules in this environment. Together, this work suggests that microvessels-on-a-chip are better models to study how TNFα harms blood vessels.

Next, systems and protocols could be develop to allow automated mass drug testing in microvessels-on-a-chip. This would help scientists to quickly screen thousands of drugs and find candidates that can protect blood vessels from TNFα.

• 3D cell culture
• endothelial cells
• human
• inflammation
• medicine
• metabolomics
• microvessels-on-a-chip
• oxidative stress

• dialysis
• nephrotoxins
• perioperative period
• renal dysfunction

• Acute Kidney Injury/etiology
• Acute Kidney Injury/physiopathology
• Acute Kidney Injury/prevention & control
• Age Factors
• Humans
• Postoperative Complications/etiology
• Postoperative Complications/physiopathology
• Postoperative Complications/prevention & control
• Renal Insufficiency, Chronic/complications
• Renal Insufficiency, Chronic/physiopathology
• Risk Assessment/methods
• Risk Reduction Behavior

Travel of unacclimatized subjects to a high altitude has been growing in popularity. Changes in endothelial shedding [circulating endothelial cells (ECs)] and hematopoietic stem and progenitor cells (CPCs) during physical exercise in hypobaric hypoxia, however, are not well understood. We investigated the change in ECs and CPCs when exposed to high altitude, after acute exercise therein, and after an overnight stay in hypobaric hypoxia in 11 healthy unacclimatized subjects. Blood withdrawal was done at baseline (520 m a.s.l.; baseline), after passive ascent to 3,883 m a.s.l. (arrival), after acute physical exercise (±400 m, postexercise) and after an overnight stay at 3,883 m a.s.l. (24 h). Mature blood cells, ECs, and CPCs were assessed by a hematology analyzer and flow cytometry, respectively. The presence of matrix metalloproteinases (MMPs), their activity, and hematopoietic cytokines were assessed in serum and plasma. EC and CPC concentrations significantly decreased after exercise (p = 0.019, p = 0.007, respectively). CPCs remained low until the next morning (24 h, p = 0.002), while EC concentrations returned back to baseline. MMP-9 decreased at arrival (p = 0.021), stayed low postexercise (p = 0.033), and returned to baseline at 24 h (p = 0.035 to postexercise). MMP-activity did not change throughout the study. Circulating MMP-9 concentrations, but not MMP-activity, were associated with EC concentrations (r_rm = 0.48, p = 0.010). CPC concentrations were not linked to hematopoietic cytokines. Acute exercise at high altitude attenuated endothelial shedding, but did not enhance regenerative CPCs. Results were not linked to endothelial matrix remodeling or CPC mobilization. These results provide information to better understand the endothelium and immature immune system during an active, short-term sojourn at high altitude.

• endothelial shedding
• hematopoietic progenitor cell
• high altitude
• matrix remodeling
• unacclimatized

Chronic kidney disease (CKD) is associated with endothelial dysfunctions thus prompting links between microcirculation (MC), inflammation and major cardiovascular risk factors.

We have previously reported that siRNA-silencing of CD40 (siCD40) reduced atherosclerosis (ATH) progression. Here, we have deepened on the effects of the siCD40 treatment by evaluating retrospectively, in stored kidneys from the siCD40 treated ApoE^−/− mice, the renal microcirculation (measured as the density of peritubular capillaries), macrophage infiltration and NF-κB activation.

Kidneys were isolated after 16 weeks of treatment with the anti-CD40 siRNA (siCD40), with a scrambled control siRNA (siSC) or with PBS (Veh. group). Renal endothelium, infiltrating macrophages and activated NF-κB in endothelium were identified by immunohistochemistry, while the density of stained peritubular capillaries was quantified by image analysis.

ATH was associated with a reduction in renal MC, an effect reversed by the anti-CD40 siRNA treatment (3.8 ± 2.7% in siCD40; vs. 1.8 ± 0.1% in siSC; or 1.9 ± 1.6% in Veh.; p < 0.0001). Furthermore, siCD40 treatment reduced the number of infiltrating macrophages compared to the SC group (14.1 ± 5.9 cells/field in siCD40; vs. 37.1 ± 17.8 cells/field in siSC; and 1.3 ± 1.7 cells/field in Veh.; p = 0.001). NF-κB activation also peaked in the siSC group, showing lower levels in the siCD40 and Veh. groups (63 ± 60 positive cells/section in siCD40; vs. 152 ± 44 positive cells/section in siSC; or 26 ± 29 positive cells/section in veh.; p = 0.014). Lastly, serum creatinine was also increased in the siCD40 (3.4 ± 3.3 mg/dL) and siSC (4.6 ± 3.0 mg/dL) groups when compared with Veh. (1.1 ± 0.9 mg/dL, p = 0.1).

Anti-CD40 siRNA therapy significantly increased the density of peritubular capillaries and decreased renal inflammation in the ATH model. These data provide a physiological basis for the development of renal diseases in patients with ATH. Furthermore, our results also highligth renal off-target effects of the siRNA treatment which are discussed.

• Atherosclerosis
• Inflammatory milieu
• Innate immunity
• Kidney
• Macrophage infiltration
• Off-target side effects
• siRNA therapy

• Adult
• Aged
• Argonaute Proteins/blood
• Biomarkers/metabolism
• Circulating MicroRNA/blood
• Diabetes Mellitus, Type 1/blood
• Diabetic Nephropathies/blood
• Extracellular Vesicles/metabolism
• Female
• Glomerular Filtration Rate/physiology
• Humans
• Lipoproteins, HDL/blood
• Male
• Middle Aged
• Renal Insufficiency, Chronic/blood

• Atherosclerosis
• Autophagy
• Microparticles
• Rheumatoid arthritis

• endothelial barrier dysfunction
• endothelial glycocalyx
• ginsenoside Rg1
• heparanase

Extracellular vesicles (EVs) are generated at increased rates from parenchymal and circulating blood cells during exposure of the circulation to abnormal flow conditions and foreign materials associated with extracorporeal circuits (ExCors). This review describes types of EVs produced in different ExCors and extracorporeal life support (ECLS) systems including cardiopulmonary bypass circuits, extracorporeal membrane oxygenation (ECMO), extracorporeal carbon dioxide removal (ECCO₂R), apheresis, dialysis and ventricular assist devices. Roles of EVs not only as biomarkers of adverse events during ExCor/ECLS use, but also as mediators of vascular dysfunction are explored. Manipulation of the number or subtypes of circulating EVs may prove a means of improving vascular function for individuals requiring ExCor/ECLS support. Strategies for therapeutic manipulation of EVs during ExCor/ECLS use are discussed such as accelerating their clearance, preventing their genesis or pharmacologic options to reduce or select which and how many EVs circulate. Strategies to reduce or select for specific types of EVs may prove beneficial in preventing or treating other EV-related diseases such as cancer.

• ECMO
• cardiopulmonary bypass
• extracellular vesicles
• extracorporeal circuits
• hemodialysis

• Animal models
• Fibrogenesis
• Fibrosis
• Glomerulosclerosis
• Kidney
• Microvasculature

• chronic kidney disease
• endothelial function
• hemodynamic
• renal function
• wall shear stress

• obesity
• overweight
• biomarkers
• kidney disease
• endothelium
• adolescents

• Adolescent
• Biomarkers/blood
• Blood Pressure/physiology
• Body Mass Index
• Brazil/epidemiology
• Cardiovascular Diseases/etiology
• Cross-Sectional Studies
• Endothelium, Vascular/physiopathology
• Female
• Humans
• Kidney Diseases/etiology
• Kidney Diseases/physiopathology
• Kidney Failure, Chronic/physiopathology
• Male
• Obesity/blood
• Obesity/complications
• Obesity/epidemiology
• Obesity/physiopathology
• Renal Insufficiency, Chronic
• Risk Factors
• Syndecan-1/blood
• Syndecan-1/urine
• Young Adult

• AKI
• NETs
• PAD4
• PAD4 inhibitor
• ischemia-reperfusion
• neutrophil transfer

• apolipoprotein A-II
• endothelium
• high density lipoprotein
• lecithin:cholesterol acyltransferase
• nitric oxide