scholarly journals Sulodexide improves endothelial dysfunction in streptozotocin-induced diabetes in rats

2008 ◽  
pp. 491-494
Author(s):  
V Kristová ◽  
S Líšková ◽  
R Sotníková ◽  
R Vojtko ◽  
A Kurtanský
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Rat Aorta ◽  
Cardiovascular Complications ◽  
Mesenteric Arteries ◽  
Circulating Endothelial Cells ◽  
Protective Effects ◽  
Pharmacological Agents ◽  
Postprandial Plasma Glucose ◽  
Streptozotocin Induced Diabetes

Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10- week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes.

scholarly journals Toll-like receptor 2 mediates high-fat diet-induced impairment of vasodilator actions of insulin

2013 ◽  
Vol 304 (10) ◽  
pp. E1077-E1088 ◽  
Author(s):  
Hyun-Ju Jang ◽  
Hae-Suk Kim ◽  
Daniel H. Hwang ◽  
Michael J. Quon ◽  
Jeong-a Kim
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
High Fat Diet ◽  
Saturated Fatty Acids ◽  
Cardiovascular Complications ◽  
Mesenteric Arteries ◽  
High Fat ◽  
Proinflammatory Response ◽  
Proinflammatory Responses ◽  
Sirna Knockdown

Obesity is characterized by a chronic proinflammatory state that leads to endothelial dysfunction. Saturated fatty acids (SFA) stimulate Toll-like receptors (TLR) that promote metabolic insulin resistance. However, it is not known whether TLR2 mediates impairment of vascular actions of insulin in response to high-fat diet (HFD) to cause endothelial dysfunction. siRNA knockdown of TLR2 in primary endothelial cells opposed palmitate-stimulated expression of proinflammatory cytokines and splicing of X box protein 1 (XBP-1). Inhibition of unfolding protein response (UPR) reduced SFA-stimulated expression of TNFα. Thus, SFA stimulates UPR and proinflammatory response through activation of TLR2 in endothelial cells. Knockdown of TLR2 also opposed impairment of insulin-stimulated phosphorylation of eNOS and subsequent production of NO. Importantly, insulin-stimulated vasorelaxation of mesenteric arteries from TLR2 knockout mice was preserved even on HFD (in contrast with results from arteries examined in wild-type mice on HFD). We conclude that TLR2 in vascular endothelium mediates HFD-stimulated proinflammatory responses and UPR that accompany impairment of vasodilator actions of insulin, leading to endothelial dysfunction. These results are relevant to understanding the pathophysiology of the cardiovascular complications of diabetes and obesity.

scholarly journals Lipoic acid antagonizes paraquat-induced vascular endothelial dysfunction by suppressing mitochondrial reactive oxidative stress

2019 ◽  
Vol 8 (6) ◽  
pp. 918-927 ◽  
Author(s):  
Li Pang ◽  
Ping Deng ◽  
Yi-dan Liang ◽  
Jing-yu Qian ◽  
Li-Chuan Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nitric Oxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Lipoic Acid ◽  
Microvascular Endothelial Cells ◽  
Ros Generation ◽  
Protective Effects ◽  
Migration Ability ◽  
Microvascular Endothelial

Abstract Paraquat (PQ) is a widely used herbicide in the agricultural field. The lack of an effective antidote is the significant cause of high mortality in PQ poisoning. Here, we investigate the antagonistic effects of alpha lipoic acid (α-LA), a naturally existing antioxidant, on PQ toxicity in human microvascular endothelial cells (HMEC-1). All the doses of 250, 500 and 1000 μM α-LA significantly inhibited 1000 μM PQ-induced cytotoxicity in HMEC-1 cells. α-LA pretreatment remarkably diminished the damage to cell migration ability, recovered the declined levels of the vasodilator factor nitric oxide (NO), elevated the expression level of endothelial nitric oxide synthases (eNOS), and inhibited the upregulated expression of vasoconstrictor factor endothelin-1 (ET-1). Moreover, α-LA pretreatment inhibited reactive oxygen species (ROS) generation, suppressed the damage to the mitochondrial membrane potential (ΔΨm) and mitigated the inhibition of adenosine triphosphate (ATP) production in HMEC-1 cells. These results suggested that α-LA could alleviate PQ-induced endothelial dysfunction by suppressing oxidative stress. In summary, our present study provides novel insight into the protective effects and pharmacological potential of α-LA against PQ toxicity in microvascular endothelial cells.

scholarly journals KLF2 is a therapeutic target for COVID-19 induced endothelial dysfunction

2021 ◽  
Author(s):  
Suowen Xu ◽  
Sihui Luo ◽  
Xueying Zheng ◽  
Jianping Weng
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Umbilical Vein ◽  
Cardiovascular Complications ◽  
Monocyte Adhesion ◽  
Sequencing Data ◽  
Atorvastatin Treatment ◽  
Tnf Α ◽  
Adhesive Molecules ◽  
Umbilical Vein Endothelial Cells

AbstractCoronavirus disease 2019 (COVID-19) is regarded as an endothelial disease (endothelialitis) with its mechanism being incompletely understood. Emerging evidence has demonstrated that the endothelium represents the Achilles' heel in COVID-19 patients and that endothelial dysfunction precipitates COVID-19 and accompanying multi-organ injuries. Thus, pharmacotherapies targeting endothelial dysfunction have potential to ameliorate COVID-19 and its cardiovascular complications. Primary human umbilical vein endothelial cells (HUVECs) and human pulmonary microvascular endothelial cells (HPMECs) were treated with serum from control subjects or COVID-19 patients. Downstream monocyte adhesion and associated gene/protein expression was evaluated in endothelial cells exposed to COVID-19 patient serum in the presence of KLF2 activator (Atorvastatin) or KLF2 overexpression by an adenoviral vector. Here, we demonstrate that the expression of KLF2 was significantly reduced and monocyte adhesion was increased in endothelial cells treated with COVID-19 patient serum due to elevated levels of pro-adhesive molecules, ICAM1 and VCAM1. IL-1β and TNF-α, two cytokines observed in cytokine release syndrome in COVID-19 patients, decreased KLF2 gene expression. Next-generation RNA-sequencing data showed that atorvastatin treatment leads to a cardiovascular protective transcriptome associated with improved endothelial function (vasodilation, anti-inflammation, antioxidant status, anti-thrombosis/-coagulation, anti-fibrosis and reduced angiogenesis). Treatment of HPMECs with atorvastatin or KLF2 adenovirus ameliorate COVID-19 serum-induced increase in endothelial inflammation and monocyte adhesion by increasing KLF2 expression. Altogether, the present study demonstrates that genetic and pharmacological activation of KLF2 represses COVID-19 associated endothelial dysfunction, heralding a potentially new direction to treat endothelialitis accompanying COVID-19.

scholarly journals Dynamics of endothelian function in different treatment strategies in stable ischemic heart disease

2019 ◽  
Vol 11 (1) ◽  
pp. 5-12
Author(s):  
Sergey A. Sayganov ◽  
Anastasiia M. Kuzmina-Krutetskaia
Keyword(s):  
Endothelial Cells ◽  
Heart Disease ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ischemic Heart Disease ◽  
Peripheral Blood ◽  
Ischemic Heart ◽  
Circulating Endothelial Cells ◽  
Lipid Lowering ◽  
Stable Ischemic Heart Disease

Aim. To assess the dynamics of endothelial function by determining circulating endothelial cells in peripheral blood in patients with stable ischemic heart disease within various treatment approaches. Material and methods. The study involved 98 patients with stable ischemic heart disease and 30 patients in the control group without coronary atherosclerosis. Endothelial function was assessed by determining the number of circulating endothelial cells in peripheral blood using flow cytofluorimetry with antibodies to cell surface markers: CD146+CD45– at the baseline. Depending on the treatment tactics, the study participants were divided into 3 groups: the medicamental therapy group, the group of coronary stenting, and the group of coronary bypass surgery. After 3 months from the baseline, dinamics assessment of endothelial dysfunction was performed. Results. Endothelial dysfunction was observed in all patients with obstructive lesions of the coronary blood flow and associated with effort angina class and anatomical severity of coronary disease. Improvement of endothelial function was facilitated by lipid-lowering therapy. Revascularization by coronary stenting impaired endothelial function in three months after the intervention. Mycoardial revascularization by coronary bypass did not impair endothelial function. Conclusion. Examination of endothelial dysfunction by determining the number of circulating endothelial cells in peripheral blood can be used to assess the severity of endothelial dysfunction in patients with IHD receiving lipid-lowering therapy and undergoing surgical revascularization.

scholarly journals Convalescent COVID-19 patients are susceptible to endothelial dysfunction due to persistent immune activation

2020 ◽  
Author(s):  
Florence WJ Chioh ◽  
Siew-Wai Fong ◽  
Barnaby E. Young ◽  
Kan-Xing Wu ◽  
Anthony Siau ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Acute Infection ◽  
Vascular Complications ◽  
Preventive Therapy ◽  
Circulating Endothelial Cells ◽  
Vascular Events ◽  
Activation Markers ◽  
The Impact

ABSTRACTThe rapid rise of coronavirus disease 2019 patients who suffer from vascular events after their initial recovery is expected to lead to a worldwide shift in disease burden. We aim to investigate the impact of COVID-19 on the pathophysiological state of blood vessels in convalescent patients. Here, convalescent COVID-19 patients with or without preexisting conditions (i.e. hypertension, diabetes, hyperlipidemia) were compared to non-COVID-19 patients with matched cardiovascular risk factors or healthy participants. Convalescent patients had elevated circulating endothelial cells (CECs), and those with underlying cardiovascular risk had more pronounced endothelial activation hallmarks (ICAM1, P-selectin or CX3CL1) expressed by CECs. Multiplex microbead-based immunoassays revealed some levels of cytokine production sustained from acute infection to recovery phase. Several proinflammatory and activated T lymphocyte-associated cytokines correlated positively with CEC measures, implicating cytokine-driven endothelial dysfunction. Finally, the activation markers detected on CECs mapped to the counter receptors (i.e. ITGAL, SELPLG, and CX3CR1) found primarily on CD8+ T cells and natural killer cells, suggesting that activated endothelial cells could be targeted by cytotoxic effector cells. Clinical trials in preventive therapy for post-COVID-19 vascular complications may be needed.Graphical abstract

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