title: Icariin attenuates cardiac remodelling through down-regulating myocardial apoptosis and matrix metalloproteinase activity in rats with congestive heart failure.
abstract: OBJECTIVE
  In this study, the anti-heart failure effect of icariin, a natural flavonol glycoside, and the underlying mechanisms were investigated.
  
  
  METHODS
  Heart failure was induced by isoproterenol in male Sprague-Dawley rats. Matrix metalloproteinase activity was determined by gelatin zymography assay. The mRNA expression was determined by real-time PCR. The protein expression was determined by Western bolt. Mitochondria structure was examined by transmission electron microscopy.
  
  
  RESULTS
  Isoproterenol administration resulted in a severe heart failure, as shown by the increased levels of left ventricular weight index, heart rate, left ventricular end diastolic pressure, maximal rate of left ventricular pressure decline (dp/dt(min) ), decreased levels of left ventricular systolic pressure and maximal rate of left ventricular pressure rise (dp/dt(max) ). Against these, icariin dose-dependently reversed the changes of these cardiac morphometric and haemodynamic parameters. In addition, icariin significantly inhibited serum levels of tumour necrosis factor-α, noradrenaline, angiotensin II and brain natriuretic peptide in rats with congestive hear failure and improved the histological changes, including cardiocyte hypertrophy, cardiocyte degeneration, inflammatory infiltration and cardiac desmoplasia. Furthermore, the expression and activity of matrix metalloproteinase (MMP)-2 and MMP-9, which regulate collagen production, were also blocked by icariin. Moreover, myocardial apoptosis was remarkably attenuated by icariin through regulating Bcl-2/Bax axle.
  
  
  CONCLUSIONS
  Icariin ameliorates left ventricular dysfunction and cardiac remodelling through down-regulating matrix metalloproteinase-2 and 9 activity and myocardial apoptosis in rats with congestive heart failure.
authors.affiliation: Department of Cardiology, The Third Affiliated Hospital of Nanjing University of Traditional Chinese Medicine Department of Integrated Traditional Chinese and Western Medicine, Nanjing General Hospital of Nanjing Military Command, Nanjing, China.
authors.forename: Yao-Hong
authors.initials: YH
authors.lastname: Song
authors.forename: Hui
authors.initials: H
authors.lastname: Cai
authors.forename: Ning
authors.initials: N
authors.lastname: Gu
authors.forename: Chun-Fa
authors.initials: CF
authors.lastname: Qian
authors.forename: Shou-Pei
authors.initials: SP
authors.lastname: Cao
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhao
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002316:Cardiotonic Agents / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology* / Q000627:therapeutic use*; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007545:Isoproterenol; D008297:Male; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000378:metabolism*; D008928:Mitochondria / Q000648:ultrastructure; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D020257:Ventricular Remodeling / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D005419:Flavonoids; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D020782:Matrix Metalloproteinases; D007545:Isoproterenol; C056599:icariin; D009638:Norepinephrine