Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) inright-sided congestive heart failure

Heme oxygenase (HO)-1 is a stress protein (HSP 32) and, together with HO-2, catalyses oxidation of the heme molecule to generate carbon monoxide, a ga s with vasodilatory properties. and bilirubin, an antioxidant. Right-sided heart failure (RHF) resulted in a two-fold increase in the HO-1 transcript (similar to 1.8 kb) in the right ventricle (RV) of RHF dogs compared to tha t of controls, In contrast, the left ventricle showed no increase in HO-1 m RNA in RHF. The change in HO was unique to HO-1, because neither the HO-2, transcripts (similar to 1.3 and 1.9 kb) nor the HSP 70 mRNA was altered in either ventricle. This increase in HO-1 mRNA in RV was accompanied by a two -fold increase in immunoreactive HO-1 protein, as judged by Western blot an alysis, as well as by a significant increase in cGMP levels. There was, how ever, no significant increase in RV total nitric oxide synthase activity in RHF. Furthermore, since norepinephrine infusion also increased HO-1 transc ript and protein levels, the HO-1 system probably was induced in RHF by the increased interstitial norepinephrine levels known to occur in failing myo cardium. This differential regulation and induction of HO-1 gene in the fai ling ventricle might be one of the defense mechanisms by which the heart at tempts to protect from stress caused by congestive heart failure. (C) 1999 Academic Press.