scholarly journals Markers of endothelial dysfunction

2017 ◽  
Vol 16 (1) ◽  
pp. 4-15 ◽  
Author(s):  
L. V. Vasina ◽  
N. N. Petrishchev ◽  
T. D. Vlasov
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Cardiovascular System ◽  
Endothelial Damage ◽  
Morphological Heterogeneity

Endothelial dysfunction is considered as a universal non-specific link in the pathogenesis of many diseases, primarily the cardiovascular system. This review is devoted to the discussion of the main functions of the endothelium and mechanisms for their implementation. One of the most striking features of endothelial cells is their morphological heterogeneity, which allows us to identify several typical forms of endothelial dysfunction (vasomotor, hemostatic, adhesion and angiogenous). Also, the review presents the most promising predictors of cardiovascular diseases and their complications among endothelial damage markers.

scholarly journals P2Y Purinergic Receptors, Endothelial Dysfunction, and Cardiovascular Diseases

2020 ◽  
Vol 21 (18) ◽  
pp. 6855 ◽  
Author(s):  
Derek Strassheim ◽  
Alexander Verin ◽  
Robert Batori ◽  
Hala Nijmeh ◽  
Nana Burns ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Cardiovascular System ◽  
G Protein ◽  
Purinergic Receptors ◽  
G Protein Coupled Receptors ◽  
Receptor Subtypes ◽  
Activated State ◽  
G Protein Coupled

Purinergic G-protein-coupled receptors are ancient and the most abundant group of G-protein-coupled receptors (GPCRs). The wide distribution of purinergic receptors in the cardiovascular system, together with the expression of multiple receptor subtypes in endothelial cells (ECs) and other vascular cells demonstrates the physiological importance of the purinergic signaling system in the regulation of the cardiovascular system. This review discusses the contribution of purinergic P2Y receptors to endothelial dysfunction (ED) in numerous cardiovascular diseases (CVDs). Endothelial dysfunction can be defined as a shift from a “calm” or non-activated state, characterized by low permeability, anti-thrombotic, and anti-inflammatory properties, to a “activated” state, characterized by vasoconstriction and increased permeability, pro-thrombotic, and pro-inflammatory properties. This state of ED is observed in many diseases, including atherosclerosis, diabetes, hypertension, metabolic syndrome, sepsis, and pulmonary hypertension. Herein, we review the recent advances in P2Y receptor physiology and emphasize some of their unique signaling features in pulmonary endothelial cells.

scholarly journals POS1065 CIRCULATING ENDOTHELIAL CELLS AS A MARKER OF CARDIOVASCULAR DISEASES IN PATIENTS WITH PSORIATIC ARTHRITIS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 811.1-811
Author(s):  
S. Smiyan ◽  
A. Bilukha ◽  
B. Koshak
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Risk ◽  
Psoriatic Arthritis ◽  
Cardiovascular Diseases ◽  
Endothelial Damage ◽  
Diagnostic Methods ◽  
Circulating Endothelial Cells ◽  
Control Group ◽  
Cardiovascular Morbidity And Mortality ◽  
Increased Risk

Background:Psoriatic arthritis (PsA) is a chronic inflammatory joint disease which develops in patients with psoriasis. Mortality among patients with PsA is 1.28 times higher than population levels and in most cases it is caused by cardio-vascular diseases (CVD). Those patients have increased risk of clinical and subclinical CVD, mostly due to endothelial dysfunction (ED) and accelerated atherosclerosis. Elevated levels of circulating endothelial cells (CEC) have been described in different cardiovascular pathologies, suggesting their potential use as diagnostic biomarkers for dysfunction of endothelium.Objectives:To identify the potential role of circulating endothelial cells as a marker of cardiovascular diseases in patients with psoriatic arthritis.Methods:In total, ninety-four patients with PsA, who fulfilled the disease criteria (CASPAR) were examined using standard diagnostic methods (including C-reactive protein (CRP), lipid profile) and evaluation endothelium-dependent vasodilation in response to reactive hyperemia (EDVD). Circulating endothelial cells were determined in the peripheral venous blood samples by flow cytometry and counted according to a standardized protocol using a fluorescence microscope after acridine orange labeling. The control group, which were consisted from thirty healthy adults were also examined.Results:CEC were quantified in patients with PsA (7,15 ± 0,19 cells mL−1) and in the control group (4,05 ± 0,11 cells mL−1). Comparing two groups of patients, endothelial circulating cell level was significantly different (p = 0.0001). Finally, we analyzed the relationship between CEC count, comorbidities, cardiovascular risk factors and EDVD in patients with PsA. Increased CEC levels were associated with obesity (r=0,62), duration of disease (r=0,65), age (r=0,67), increased CRP (r=0,76), high blood pressure (r=0,87) and decreased EDVD (r=–0,91).Conclusion:CEC counts were significantly higher in patients with PsA, positively correlated with the main factors of CVD, and another specific marker of ED - EDVD. Elevated CEC levels were also associated with high concentrations of CRP, which plays a direct role in promoting vascular inflammation, vessel damage and clinical CVD events. In conclusion, increased CEC counts provide a direct proof of endothelial damage in patient with PsA and a clinically informative diagnostic tool for endothelial damage in pre-symptomatic CVD. As CEC are one of the most sensitive biomarker for ED, further efforts should concentrate on improving the sensitivity of its detection in order to increase diagnostic sensitivity.References:[1]Maura Farinacci, Thomas Krahn, Wilfried Dinh, et al. Circulating endothelial cells as biomarker for cardiovascular diseases. Res Pract Thromb Haemost, Vol. 3, Issue, 2019, P.49-58;[2]C. Horreau, C. Pouplard, E. Brenautet, et al. Cardiovascular morbidity and mortality in psoriasis and psoriatic arthritis: a systematic literature review. J Eur Acad Dermatol Venereol, Vol. 27, Issue 3, 2013, P.12-19;[3]Frank Verhoeven, Clément Prati, Céline Demougeot, Daniel Wendling. Cardiovascular risk in psoriatic arthritis, a narrative review. Joint Bone Spine, Vol. 87, Issue 5, 2020, P.413-418;Disclosure of Interests:None declared.

scholarly journals Evolving Role of Microparticles in the Pathophysiology of Endothelial Dysfunction

2013 ◽  
Vol 59 (8) ◽  
pp. 1166-1174 ◽  
Author(s):  
Fina Lovren ◽  
Subodh Verma
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Vascular Endothelial Cells ◽  
Current Knowledge ◽  
Early Event ◽  
Prognostic Information ◽  
Vascular Events ◽  
Wide Range

BACKGROUND Endothelial dysfunction is an early event in the development and progression of a wide range of cardiovascular diseases. Various human studies have identified that measures of endothelial dysfunction may offer prognostic information with respect to vascular events. Microparticles (MPs) are a heterogeneous population of small membrane fragments shed from various cell types. The endothelium is one of the primary targets of circulating MPs, and MPs isolated from blood have been considered biomarkers of vascular injury and inflammation. CONTENT This review summarizes current knowledge of the potential functional role of circulating MPs in promoting endothelial dysfunction. Cells exposed to different stimuli such as shear stress, physiological agonists, proapoptotic stimulation, or damage release MPs, which contribute to endothelial dysfunction and the development of cardiovascular diseases. Numerous studies indicate that MPs may trigger endothelial dysfunction by disrupting production of nitric oxide release from vascular endothelial cells and subsequently modifying vascular tone. Circulating MPs affect both proinflammatory and proatherosclerotic processes in endothelial cells. In addition, MPs can promote coagulation and inflammation or alter angiogenesis and apoptosis in endothelial cells. SUMMARY MPs play an important role in promoting endothelial dysfunction and may prove to be true biomarkers of disease state and progression.

Abstract 18673: JNK Inhibition Restores Endothelial Function in Type 2 Diabetes Mellitus

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Rosa Breton-Romero ◽  
Bihua Feng ◽  
Monika Holbrook ◽  
Melissa G Farb ◽  
Jessica L Fetterman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Diabetic Patients ◽  
Jnk Activation

Introduction: Diabetes mellitus type 2 is an increasingly public health problem and it is a major cause in the development of cardiovascular diseases. Endothelial dysfunction is a key mechanism that contributes to the pathogenesis of cardiovascular diseases and is a well-known feature of clinical diabetes. Prior studies have demonstrated an impaired nitric oxide bioavailability and a reduced endothelium-dependent vasodilation under diabetic conditions and in animal models, JNK activity has been widely described to be involved in systemic insulin resistance. Hypothesis: Our study aimed to evaluate the involvement of JNK in endothelial dysfunction, studying its potential role in altered eNOS activation and NO synthesis in diabetic patients. Methods: We measured endothelial function and JNK activity in freshly isolated endothelial cells from diabetic patients (n=38) and nondiabetic controls (n=40). Results: ECs from diabetic patients displayed impaired eNOS activation and reduced NO release after insulin and A23187 stimulation, consistent with the presence of endothelial dysfunction. JNK activation was higher in diabetic (**P=0.003), and was associated with lower flow-mediated dilation (r=-0.53, *P=0.02). In endothelial cells from diabetic patients, treatment with JNK chemical inhibitor (SP600125) restored eNOS activation and insulin response (***P<0.001). Nitric oxide bioactivity after A23187 stimuli with diabetes was also recovered in endothelial cells from patients with diabetes. Conclusions: In summary, our data suggest that JNK activation contributes to vascular insulin resistance and endothelial dysfunction in patients with type 2 diabetes and may represent a target in novel therapeutic opportunities.

scholarly journals Circulating Endothelial Cells and Chronic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Kunying Zhang ◽  
Fang Yin ◽  
Lin Lin
Keyword(s):  
Chronic Kidney Disease ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
Vascular Dysfunction ◽  
Endothelial Damage ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Term Outcome ◽  
Long Term Outcome

Endothelial dysfunction may play a crucial role in initiation of the pathogenesis of vascular disease and atherosclerosis. The identification and quantification of circulating endothelial cells (CEC) have been developed as a novel marker of endothelial function. We describe, in great detail, mechanisms of endothelial dysfunction and CEC detachment. We also review the relationship between numbers of CEC and disease severity and response to treatment. In addition, we describe the possible clinical use of CEC in chronic kidney disease (CKD) and kidney transplantation. In summary, CEC have been developed as a novel approach to assess the endothelial damage. Measurement of the CEC level would provide an important diagnostic and prognostic value on the endothelium status and the long-term outcome of vascular dysfunction.

Endothelial dysfunction as a cellular mechanism for vascular failure

2012 ◽  
Vol 302 (3) ◽  
pp. H499-H505 ◽  
Author(s):  
Tetsuaki Hirase ◽  
Koichi Node
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Barrier Function ◽  
Molecular Mechanisms ◽  
Vascular Dysfunction ◽  
Small Gtpases ◽  
Cellular Mechanism ◽  
Cell Junctions ◽  
Microtubule Function

The regulation of vascular tone, vascular permeability, and thromboresistance is essential to maintain blood circulation and therefore tissue environments under physiological conditions. Atherogenic stimuli, including diabetes, dyslipidemia, and oxidative stress, induce vascular dysfunction, leading to atherosclerosis, which is a key pathological basis for cardiovascular diseases such as ischemic heart disease and stroke. We have proposed a novel concept termed “vascular failure” to comprehensively recognize the vascular dysfunction that contributes to the development of cardiovascular diseases. Vascular endothelial cells form the vascular endothelium as a monolayer that covers the vascular lumen and serves as an interface between circulating blood and immune cells. Endothelial cells regulate vascular function in collaboration with smooth muscle cells. Endothelial dysfunction under pathophysiological conditions contributes to the development of vascular dysfunction. Here, we address the barrier function and microtubule function of endothelial cells. Endothelial barrier function, mediated by cell-to-cell junctions between endothelial cells, is regulated by small GTPases and kinases. Microtubule function, regulated by the acetylation of tubulin, a component of the microtubules, is a target of atherogenic stimuli. The elucidation of the molecular mechanisms of endothelial dysfunction as a cellular mechanism for vascular failure could provide novel therapeutic targets of cardiovascular diseases.

scholarly journals Sulodexide. Prophylactic and therapy response to endothelial dysfunction

2015 ◽  
Vol 4 (4S) ◽  
pp. 23-32
Author(s):  
Luca Masotti
Keyword(s):  
Oxidative Stress ◽  
Clinical Trials ◽  
Endothelial Cells ◽  
Diabetic Nephropathy ◽  
Endothelial Dysfunction ◽  
Cardiovascular System ◽  
Diabetic Foot ◽  
Therapy Response ◽  
Protective Properties

Endothelial dysfunction plays the key role in the development of cardiovascular system disorders. Sulodexide, decreasing oxidative stress and stabilizing endothelial cells, has protective properties on endothelial dysfunction. The article describes the role of sulodexide both in prophylaxis and therapy of venous and arterial diseases, underlining its clinical efficacy as demonstrated in clinical trials. Besides, the article describes its role in the management of some other diseases, like diabetic nephropathy, diabetic foot, tinnitus, or hemorrhoids.

Evidence of Endothelial Dysfunction in Cocaine Users.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1891-1891 ◽  
Author(s):  
Jai me Pereira ◽  
Claudia G. Sáez ◽  
Julio Pallavicini ◽  
Paulina Olivares ◽  
Olga Panes ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Vascular Disease ◽  
Von Willebrand Factor ◽  
Peripheral Blood ◽  
Endothelial Damage ◽  
Cocaine Users ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Plasma Markers

Abstract Background: Cocaine abuse is associated with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. In this sense, in vitro studies have demonstrated that cocaine may induce damage and/or activation of endothelial cells. The structural and functional integrity of the endothelium is essential for the maintenance of vascular homeostasis and its damage plays a critical role in the pathogenesis of vascular disease. Endothelial dysfunction may be assessed by testing the impaired vasodilator response to a stimulus or by measuring the release of plasma markers of endothelial damage. Increased number of circulating endothelial cells (CECs) has been reported in several pathologic conditions associated with severe vascular damage and its enumeration in peripheral blood is currently considered a reliable method to assess endothelial damage. We hypothesized that chronic exposure to cocaine induces endothelial damage which could be expressed by increased CEC counts in peripheral blood. Methods: Twenty cocaine-dependent subjects (aged 19–52 years, mean age 30 years) and 25 healthy, matched controls (aged 20–49 years, mean age 31 years) were studied; all patients fulfilled DSM-IV criteria for cocaine dependence with drug exposure within the 72 hours prior to blood sampling. CECs were isolated from peripheral blood by use of immunomagnetic beads coated with anti-CD146, stained for CD45 and Ulex Europaeus lectin 1 and counted under fluorescence microscopy. MCP-1, sICAM-1, von Willebrand factor and high-sensitivity C-reactive protein (hsCRP) were measured by enzyme-linked immunosorbent assay. Results: Compared to controls, CECs were significantly elevated among cocaine users (632 ± 281 vs 67 ± 54 cells/mL, p&lt;0.0001). Plasma levels of sICAM-1 (360±92 ng/mL) and MCP-1 (166±71 pg/mL) were increased in cocaine-dependent individuals compared to the controls (261±34 and 67±29, respectively; p&lt; 0.01). The hsCRP levels were significantly increased (6.8 mg/L); however plasma von Willebrand factor concentration was not different between patients and controls (86.4±22 vs 70.5±16%, respectively; NS). Levels of CECs correlated positively with sICAM-1 (r: 0.7; p: 0.003) and hsCRP (r: 0.56; p: 0.0037). Conclusions: Highly increased number of CECs and significant increments in soluble plasma markers of endothelial perturbation were found in cocaine dependent individuals. This is the first demonstration of endothelial dysfunction among these individuals and our findings support the notion that cocaine-induced endothelial damage may play a pathogenic role in the ischemic vascular disease observed in chronic cocaine users.

A G protein–biased S1P1 agonist, SAR247799, protects endothelial cells without affecting lymphocyte numbers

2020 ◽  
Vol 13 (634) ◽  
pp. eaax8050 ◽  
Author(s):  
Bruno Poirier ◽  
Veronique Briand ◽  
Dieter Kadereit ◽  
Matthias Schäfer ◽  
Paulus Wohlfart ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
G Protein ◽  
Ischemia Reperfusion Injury ◽  
Tissue Injury ◽  
Ischemia Reperfusion ◽  
Vascular Diseases ◽  
Endothelial Damage ◽  
Renal Protection ◽  
And Function

Endothelial dysfunction is a hallmark of tissue injury and is believed to initiate the development of vascular diseases. Sphingosine-1 phosphate receptor-1 (S1P1) plays fundamental physiological roles in endothelial function and lymphocyte homing. Currently available clinical molecules that target this receptor are desensitizing and are essentially S1P1 functional antagonists that cause lymphopenia. They are clinically beneficial in autoimmune diseases such as multiple sclerosis. In patients, several side effects of S1P1 desensitization have been attributed to endothelial damage, suggesting that drugs with the opposite effect, namely, the ability to activate S1P1, could help to restore endothelial homeostasis. We found and characterized a biased agonist of S1P1, SAR247799, which preferentially activated downstream G protein signaling to a greater extent than β-arrestin and internalization signaling pathways. SAR247799 activated S1P1 on endothelium without causing receptor desensitization and potently activated protection pathways in human endothelial cells. In a pig model of coronary endothelial damage, SAR247799 improved the microvascular hyperemic response without reducing lymphocyte numbers. Similarly, in a rat model of renal ischemia/reperfusion injury, SAR247799 preserved renal structure and function at doses that did not induce S1P1-desensitizing effects, such as lymphopenia and lung vascular leakage. In contrast, a clinically used S1P1 functional antagonist, siponimod, conferred minimal renal protection and desensitized S1P1. These findings demonstrate that sustained S1P1 activation can occur pharmacologically without compromising the immune response, providing a new approach to treat diseases associated with endothelial dysfunction and vascular hyperpermeability.

Abstract 268: Adiponectin Ameliorates Palmitate Acid Induced Endothelial Inflammation in Endothelial Cells

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Xiuping Chen ◽  
Wenwen Zhao ◽  
Xuenong Zhang ◽  
Chuanhong Wu
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Diseases ◽  
Endothelial Dysfunction ◽  
Protein Expression ◽  
Mrna Expression ◽  
Technology Development ◽  
Umbilical Vein ◽  
Early Event ◽  
Development Fund ◽  
Tnf Α

Endothelial dysfunction (ED) is considered an early event of cardiovascular diseases including hypertension, atherosclerosis and so on. Inflammation participates centrally in all stages of cardiovascular diseases and is considered as a hallmark of endothelial dysfunction. In this study, the effect of adiponectin (APN), an adipocytokine derived mainly from adipocytes, on palmitate acid (PA)-induced inflammation in endothelial cells. Human umbilical vein endothelial cells (HUVECs) were treated with PA with or without APN pretreatment. The mRNA expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and ICAM-1 were measured with RT-PCR. The protein expression of ICAM-1, NOX1, NOX2, NOX4, and phosphorylation of MAPKs (JNK, ERK, and p38MAPK), IKKβ, p65 NF-κB were determined by Western blotting. Intracellular reactive oxygen species (ROS) and nitric oxide (NO) formation were determined with DCFH2-DA and DAF-FM respectively. APN significantly ameliorated PA-induced mRNA expression of TNF-α, IL-6 and ICAM-1 and protein expression of ICAM-1, NOX2, and phosphorylation of IKKβ, p65 NF-κB, p38MAPK, without affecting NOX2 and phosphorylation of JNK and ERK. APN also partly reversed PA induced ROS formation and NO decrease. NAC, a ROS scavenger, showed similar activities. The p38MAK inhibitor, SB203580, also reversed PA induced protein expression of ICAM-1 and mRNA expression of TNF-α, IL-6 and ICAM-1. Taken together, these results showed that APN improved PA induced endothelial dysfunction by regulating ROS/p38MAK/NF-κB pathways. Acknowledgement: This study was supported by the National Natural Science Foundation of China (No. 81160048) and the Science and Technology Development Fund of Macau Special Administrative Region (No. 021/2012/A1).

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