Inhibiting anti-angiogenic VEGF165b activates a miR-17-20a-Calcipressin-3 pathway that revascularizes ischemic muscle in peripheral artery disease.

ABSTRACT:

Background

VEGF₁₆₅a increases the expression of the microRNA-17-92 cluster, promoting developmental, retinal, and tumor angiogenesis. We have previously shown that VEGF₁₆₅b, an alternatively spliced anti-angiogenic VEGF-A isoform, inhibits the VEGFR-STAT3 pathway in ischemic endothelial cells (ECs) to decrease their angiogenic capacity. In ischemic macrophages (Møs), VEGF₁₆₅b inhibits VEGFR1 to induce S100A8/A9 expression, which drives M1-like polarization. Our current study aims to determine whether VEGF₁₆₅b inhibition promotes perfusion recovery by regulating the microRNA(miR)-17-92 cluster in preclinical PAD.

Methods

Femoral artery ligation and resection was used as a preclinical PAD model. Hypoxia serum starvation (HSS) was use

SUBMITTER: Batan S 

PROVIDER: S-EPMC10770062 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature