Pioglitazone inhibits HIF-1α-dependent angiogenesis in rats by paracrine and direct effects on endothelial cells.

ABSTRACT:

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Pioglitazone was associated with increased hazard for surgical or percutaneous lower extremity revascularization in patients with diabetes in a large clinical trial, but this clinical finding has not been adequately explored in animal models. We hypothesized that pioglitazone would decrease hypoxia-inducible factor 1α (HIF-1α)-dependent angiogenesis in rat ischemic hindlimb models by altering mitochondrial-derived signals supporting HIF-1α activation. We tested oral pioglitazone (10 mg/kg/day) versus placebo in two cohorts of rats with hindlimb ischemia (normal Sprague-Dawley rats and insulin-resistant JCR:La-cp rats), and evaluated direct and paracrine effects of pioglitazone on angiogenesis in vitro using human skeletal muscle and endothelial cells. Pioglitazone treatm

SUBMITTER: Dromparis P 

PROVIDER: S-EPMC3989538 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature