Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Hypoxia-inducible factor (HIF)-1α is essential following a myocardial infarction (MI), and diabetic patients have poorer prognosis post-MI. Could HIF-1α activation be abnormal in the diabetic heart, and could metabolism be causing this? Diabetic hearts had decreased HIF-1α protein following ischemia, and insulin-resistant cardiomyocytes had decreased HIF-1α-mediated signaling and adaptation to hypoxia. This was due to elevated fatty acid (FA) metabolism preventing HIF-1α protein stabilization. FAs exerted their effect by decreasing succinate concentrations, a HIF-1α activator that inhibits the regulatory HIF hydroxylase enzymes. In vivo and in vitro pharmacological HIF hydroxylase inhibition restored HIF-1α accumulation and improved post-ischemic functional recovery in diabetes.

Original publication




Journal article


JACC Basic Transl Sci

Publication Date





485 - 498


ANOVA, analysis of variance, BSA, bovine serum albumin, DMF, dimethyl fumarate, DMOG, dimethyloxalylglycine, FA, fatty acid, FIH, factor inhibiting hypoxia-inducible factor, HIF, hypoxia-inducible factor, HIF-1α, IR, insulin resistance/resistant, MI, myocardial infarction, PHD, prolyl hydroxylase domain, SSO, sulfo-N-succinimidyl oleate, cardiovascular disease, diabetes, fatty acids, hypoxia, i.p., intraperitoneal, metabolism