నైరూప్య

Promotes a coronary in Acute Cardiovascular Cells via Modulating Transcription

Brijesh Singh*

Diabetes mellitus has a higher incidence of cardiovascular disease, including Impaired microcirculation in the lower extremities where angiogenic disturbances are the main factor. The endothelium acts as a barrier between the blood and the vascular wall. Dysfunction of vascular endothelial cells by hyperglycemia is a major factor leading to impaired angiogenesis. Hydrogen sulfide (H2S) and miR-126-3p are known for their pro-angiogenic effects. However, little is known about how H2S regulates miR-126-3p to promote angiogenesis under high glucose conditions. The primary aim of this study was to investigate how H2S regulates miR-126-3p levels under high glucose conditions. We evaluated the pro-angiogenic effect of H2S in the diabetic hindlimb of an ischemic mouse model and in vivo Matrigel plugs. Using two microRNA datasets, we searched for microRNAs regulated by both diabetes and H2S. mRNA and protein levels were detected by real-time PCR and western blot, respectively. Immunofluorescence staining has also been used to determine capillary density and assess protein levels in vascular endothelial cells. We demonstrated endothelial cell migration capacity using a scratch wound healing assay. Immunoprecipitation of methylated DNA combined with real-time PCR was chosen to determine the extent of DNA methylation in HUVEC. Exogenous H2S enhanced angiogenesis in diabetic mice. Exogenous H2S restored endothelial cell migration velocity by upregulating miR-126-3p levels and downregulating high glucose elevation DNMT1 protein levels. Moreover, DNMT1 upregulation in HUVEC increased the methylation level of gene sequences upstream of miR-126-3p, which subsequently inhibited transcription of primary miR-126 and reduced miR-126-3p levels paddy field. Overexpression of CSE in HUVEC rescued miR-126-3p levels by reducing methylation levels and promoting translocation. H2S increases miR-126-3p levels by downregulating methylation levels by reducing high glucose-induced DNMT1 protein levels, thereby ameliorating angiogenesis originally impaired by high glucose.