title: Upregulating the heme oxygenase system suppresses left ventricular hypertrophy in adult spontaneously hypertensive rats for 3 months.
abstract: BACKGROUND
  Aldosterone and phospholipase C (PLC) stimulate nuclear factor-kappaB (NF-kappaB) and activating-protein (AP-1), causing fibrosis and hypertrophy. Besides harboring binding sites for NF-kappaB and AP-1, heme oxygenase (HO-1) generates cytoprotective products, including bilirubin and ferritin. The multifaceted interaction between HO-1 and aldosterone-PLC profibrotic axis in cardiac hypertrophy of spontaneously hypertensive rats (SHR) was studied.
  
  
  RESULTS
  HO-1 was induced with hemin or blocked with chromium mesoporphyrin (CrMP). The study groups included: (A) controls (SHR, WKY, and SD), (B) SHR+hemin, (C) SHR+hemin+CrMP, (D) SHR+CrMP, and (E) SHR+vehicle. Histological and morphological/morphometrical, quantitative reverse transcription-polymerase chain reaction, Western blot, enzyme immunoassay, and spectrophotometric assays were used to assess the effect of the HO system on cardiac hypertrophy. Hemin therapy evoked a 3-month enduring cardioprotection in adult SHR by lowering blood pressure, and reducing left-to-right ventricular ratio, left ventricular wall-thickness, and left ventricle-to-body-weight ratio, whereas CrMP exacerbated cardiac fibrosis/hypertrophy. The cardioprotection was accompanied by reduced aldosterone, PLC, inositol-triphosphate, NF-kappaB, AP-1, heme, and 8-isoprostane, a marker of oxidative stress, whereas HO-1, HO activity, cGMP, bilirubin, ferritin, superoxide dismutase, and the total antioxidant capacity were increased. Correspondingly, extracellular matrix/remodeling proteins such as fibronectin, collagen-1, collagen-IV, alongside cardiac histopathological lesions including fibrosis, scarring, muscular-hypertrophy, coronary-arteriolar thickening, and interstitial/perivascular collagen deposition were attenuated.
  
  
  CONCLUSIONS
  Our study unveils sustained cardioprotection by hemin that may have clinical relevance.
authors.affiliation: Department of Physiology, University of Saskatchewan College of Medicine, Saskatoon, SK, Canada. joseph.ndisang@usask.ca
authors.forename: Joseph Fomusi
authors.initials: JF
authors.lastname: Ndisang
authors.forename: Ashok
authors.initials: A
authors.lastname: Jadhav
mesh_terms: D000367:Age Factors; D000818:Animals; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis*; D006427:Hemin / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy / Q000201:enzymology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D006427:Hemin; D006419:Heme Oxygenase (Decyclizing)