THE ROLE OF HEME REGULATORY ENZYMES IN MYOCYTES UNDER STRESS

Abstract

The heme metabolism pathway remains a novel therapeutic target for heart failure treatment. However, how heme is regulated in the failing heart remains to be understood. To investigate the molecular mechanisms underlying heme regulation and its potential modulation by hypoxia inducible transcription factors, we investigated the expression of heme regulatory enzymes and hypoxia inducible factors in clinical heart failure and experimental heart failure rodent models. Here we show that heme regulatory enzymes - delta-aminolevulinic acid synthases (ALAS) and heme oxygenases (HMOX) - and heme bioavailability changed significantly in clinical and experimental rodent models of heart failure over time, that (HMOX1) protein levels remained relatively unchanged or decreased in experimental heart failure, and that HMOX1 expression is induced synergistically in heme-replete hypoxia, likely by hypoxia inducible factor 2a (HIF2a).