Apelin prevents diabetes-induced poor collateral vessel formation and blood flow reperfusion in ischemic limb
نویسندگان
چکیده
Introduction Peripheral arterial disease (PAD) is a major risk factor for lower-extremity amputation in diabetic patients. Unfortunately, previous clinical studies investigating therapeutic angiogenesis using the vascular endothelial growth (VEGF) have shown disappointing results patients, which evokes necessity novel agents. The apelinergic system (APJ receptor/apelin) highly upregulated under hypoxic condition and acts as an activator of angiogenesis. Apelin treatment improves revascularization nondiabetic models ischemia, however, its role on conditions remains poorly investigated. This study explored impact Pyr-apelin-13 cell function mouse model hindlimb ischemia. Methods Nondiabetic mice underwent femoral artery ligation to induce limb Diabetic were implanted subcutaneously with osmotic pumps delivering 28 days. Blood flow reperfusion was measured 4 weeks post-surgery exercise willingness assessed voluntary wheels. In vitro, bovine aortic cells (BAECs) exposed normal (NG) or high glucose (HG) levels hypoxia. Cell migration, proliferation tube formation assays performed following either VEGF stimulation. Results Discussion Following blood reperfusion, functional recovery density improved receiving compared untreated mice. cultured BAECs, exposure HG concentrations hypoxia reduced proangiogenic actions, whereas apelin effects remained unaltered. induced actions through Akt/AMPK/eNOS RhoA/ROCK signaling pathways both NG exposure. Our identified potential target angiogenic therapy patients PAD.
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ژورنال
عنوان ژورنال: Frontiers in Cardiovascular Medicine
سال: 2023
ISSN: ['2297-055X']
DOI: https://doi.org/10.3389/fcvm.2023.1191891