Ang-1 gene therapy inhibits hypoxia-inducible factor-1alpha (HIF-1alpha)-prolyl-4-hydroxylase-2, stabilizes HIF-1alpha expression, and normalizes immature vasculature in db/db mice.

ABSTRACT:

Objective

Diabetic impaired angiogenesis is associated with impairment of hypoxia-inducible factor-1alpha (HIF-1alpha) as well as vasculature maturation. We investigated the potential roles and intracellular mechanisms of angiopoietin-1 (Ang-1) gene therapy on myocardial HIF-1alpha stabilization and vascular maturation in db/db mice.

Research design and methods

db/db mice were systemically administrated adenovirus Ang-1 (Ad-CMV-Ang-1). Myocardial HIF-1alpha, vascular endothelial growth factor (VEGF), hemeoxygenase-1 (HO-1), endothelial nitric oxide synthase (eNOS), Akt, and HIF-1alpha-prolyl-4-hydroxylase-2 (PHD)2 expression were measured. Vasculature maturation, capillary and arteriole densities, and cardiac interstitial fibrosis were analyzed in the border zone of infarcte

SUBMITTER: Chen JX 

PROVIDER: S-EPMC2584141 | biostudies-literature | 2008 Dec

REPOSITORIES: biostudies-literature