Nitrative Stress Participates in Endothelial Progenitor Cell Injury in Hyperhomocysteinemia

Abstract

In order to investigate the role of nitrative stress in vascular endothelial injury in hyperhomocysteinemia (HHcy), thirty healthy adult female Wistar rats were randomly divided into three groups: control, hyperhomocysteinemia model, and hyperhomocysteinemia with FeTMPyP (peroxynitrite scavenger) treatment. The endothelium-dependent dilatation of thoracic aorta in vitro was determined by response to acetylcholine (ACh). The histological changes in endothelium were assessed by HE staining and scanning electron microscopy (SEM). The expression of 3-nitrotyrosine (NT) in thoracic aorta was demonstrated by immunohistochemistry and immunofluorescence, and the number of circulating endothelial progenitor cells (EPCs) was quantified by flow cytometry. Hyperhomocysteinemia caused significant endothelial injury and dysfunction including vasodilative and histologic changes, associated with higher expression of NT in thoracic aorta. FeTMPyP treatment reversed these injuries significantly. Further, the effect of nitrative stress on cultured EPCs in vitro was investigated by administering peroxynitrite donor (3-morpholino-sydnonimine, SIN-1) and peroxynitrite scavenger (FeTMPyP). The roles of nitrative stress on cell viability, necrosis and apoptosis were evaluated with 3-(4,5-dimethylthiazol)-2,5-diphenyl tetrazolium (MTT) assay, lactate dehydrogenase (LDH) release assay and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, respectively. Also, the phospho-eNOS expression and tube formation in Matrigel of cultured EPCs was detected. Our data showed that the survival of EPCs was much lower in SIN-1 group than in vehicle group, both the apoptosis and necrosis of EPCs were much more severe, and the p-eNOS expression and tube formation in Matrigel were obviously declined. Subsequent pretreatment with FeTMPyP reversed these changes. Further, pretreatment with FeTMPyP reversed homocysteine-induced EPC injury. In conclusion, this study indicates that nitrative stress plays a role in vascular endothelial injury in hyperhomocysteinemia, as well as induces endothelial progenitor cell injury directly.

Homocysteine and hydrogen sulfide in epigenetic, metabolic and microbiota related renovascular hypertension

“…This association was later concluded as weak, in part, due to inaccurate blood pressure measurement and may have confounded by renal function [137]. Mechanisms that are surfaced in the literature based on animal studies include arterial stiffness, endothelial dysfunction, decreased bioavailability of nitric oxide (NO), increased oxidative stress and peroxynitrite formation [138, 139]. Interestingly, in a cross-sectional study it was estimated that higher plasma homocysteine levels at baseline were associated with an increased, but non-significant risk of incidental hypertension in men [140].…”

Chronic Psychological Stress Accelerates Vascular Senescence and Impairs Ischemia‐Induced Neovascularization: The Role of Dipeptidyl Peptidase‐4/Glucagon‐Like Peptide‐1‐Adiponectin Axis

“…Patients under moderate or high stress at the time of an acute myocardial infarction exhibited increased 2‐year mortality compared with control subjects under low levels of stress . It was also reported that endothelial cells (ECs) and endothelial progenitor cells (EPCs) are sensitive to various pathological stressors . However, the changes in vascular aging and regenerative capacity under chronic stress conditions remain largely unknown.…”

“…stressors. [8][9][10] However, the changes in vascular aging and regenerative capacity under chronic stress conditions remain largely unknown.…”

Voltage-Dependent Anion Channel 1(VDAC1) Participates the Apoptosis of the Mitochondrial Dysfunction in Desminopathy

“…The frozen sections of the skeletal muscle of desminopathy patients and desminopathy rat model were prepared for conventional stain, containing hematoxylin and eosin (HE), Gomori Trichrome (MGT), (PAS), red oil (ORO), NADH-TR, SDH stain, the method of these staining followed the previously published [24]. …”