Heme Oxygenase‐1 Attenuates Isoproterenol‐induced Cardiac Hypertrophy in vivo

Abstract

Heme oxygenase‐1 (HO‐1) is an oxidative stress responsive gene that is implicated in protection against many pathophysiological processes including ischemia reperfusion injury and heart failure. As elevated activity of the sympathetic nerve system is a common feature of heart failure, the present study was designed to investigate the role of HO‐1 in cardiac hypertrophy during chronic β‐adrenoceptor stimulation. Isoproterenol was administered to wild type, non‐transgenic or transgenic cardiac specific HO‐1 overexpressing (α‐MHC‐HO‐1) FVB mice for 15 or 30 days at a rate of 30 μg/g/day. Chronic isoproterenol infusion caused a significant increase in left ventricular cardiac mass in the non‐transgenic but not transgenic mice (mg/g heart to body weight ratio: sham 4.9 ± 0.4, isoproterenol 6.4 ± 1.3; and sham 5.9 ± 0.7, isoproterenol 5.8 ± 0.5 for non‐transgenic and transgenic mice, respectively). Isoproterenol‐induced cardiac hypertrophy was accompanied by an increase in ventricular end diastolic pressure (P < 0.05), myocardial fibrosis and superoxide generation as measured by NADH oxidase activity. These data suggest that HO‐1 alleviates oxidative stress and cardiac hypertrophy under excessive β‐adrenergic stimulation, and that overexpression of HO‐1 is beneficial for sympatho‐excitatory cardiac hypertrophy and failure in mice. This work was supported by the Heart and Stroke Foundation of Canada.