Chamber-specific regulation of heme oxygenase-1 (heat shock protein 32) in right-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 gas with vasodilatory properties, and bilirubin, an antioxidant. Right-sided heart failure (RHF) resulted in a two-fold increase in the HO-1 transcript (;1.8 kb) in the right ventricle (RV) of RHF dogs compared to that of controls. In contrast, the left ventricle showed no increase in HO-1 mRNA in RHF. The change in HO was unique to HO-1, because neither the HO-2 transcripts (;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 analysis, as well as by a significant increase in cGMP levels. There was, however, no significant increase in RV total nitric oxide synthase activity in RHF. Furthermore, since norepinephrine infusion also increased HO-1 transcript and protein levels, the HO-1 system probably was induced in RHF by the increased interstitial norepinephrine levels known to occur in failing myocardium. This differential regulation and induction of HO-1 gene in the failing ventricle might be one of the defense mechanisms by which the heart attempts to protect from stress caused by congestive heart failure.
Raju
V S
VS
Cardiology Unit, Department of Medicine, Rochester, New York, 14642, USA. raju_vulapalli@urmc.rochester.edu
Imai
N
N
Liang
C S
CS
D000818:Animals; D004285:Dogs; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000201:enzymology* / Q000473:pathology; D006352:Heart Ventricles / Q000378:metabolism* / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay
D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1