title: Heme oxygenase-1 inhibits angiotensin II-induced cardiac hypertrophy in vitro and in vivo.
abstract: BACKGROUND
  Heme oxygenase-1 (HO-1) is a stress-response enzyme implicated in cardioprotection. To explore whether HO-1 has a role in cardiac remodeling response, the effect of its overexpression on angiotensin II (Ang II)-induced cardiac hypertrophy was examined.
  
  
  RESULTS
  HO-1 was induced in cultured rat neonatal cardiomyocytes by treatment with cobalt protoporphyrin IX (CoPPIX) or a recombinant adenovirus carrying the human HO-1 gene. Ang II-induced myocyte hypertrophy assessed by increments in cell size, [3H]leucine uptake, and protein content was suppressed by HO-1 overexpression. Cotreatment of cells with tin protoporphyrin IX, a HO inhibitor, significantly reversed the suppressive effect of HO-1. Bilirubin, one of the byproducts of heme degradation by HO-1, mediated the suppressive effect through the inhibition of Ang II-induced production of reactive oxygen species, as detected by a 2',7'-dichlorofluorescein probe. The antihypertrophic effect of HO-1 was also demonstrated in rats receiving chronic Ang II infusions. Cotreatment of animals with CoPPIX significantly attenuated Ang II-induced left ventricular hypertrophy and hyperdynamic contractions, whereas concomitant treatment with tin protoporphyrin IX abolished CoPPIX-mediated cardioprotection in vivo.
  
  
  CONCLUSIONS
  HO-1 attenuates Ang II-induced cardiac hypertrophy both in vitro and in vivo, and bilirubin mediates, at least in part, the antihypertrophic effect of HO-1 via inhibition of reactive oxygen species production after Ang II stimulation.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, Republic of China.
authors.forename: Chien-Ming
authors.initials: CM
authors.lastname: Hu
authors.forename: Yen-Hui
authors.initials: YH
authors.lastname: Chen
authors.forename: Ming-Tsai
authors.initials: MT
authors.lastname: Chiang
authors.forename: Lee-Young
authors.initials: LY
authors.lastname: Chau
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001663:Bilirubin / Q000502:physiology; D006332:Cardiomegaly / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism / Q000502:physiology*; D051547:Heme Oxygenase-1; D008297:Male; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D000804:Angiotensin II; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001663:Bilirubin