title: Basic fibroblast growth factor inhibits ventricular remodeling in Dahl salt-sensitive hypertensive rats.
abstract: OBJECTIVE
  Basic fibroblast growth factor (bFGF) inhibits the progression of ventricular remodeling in ischemic and hypertensive heart diseases (HHDs). Recent studies have revealed that bFGF induces the transition from myofibroblasts to fibroblasts with decreased expression of alpha-smooth muscle actin (alpha-SMA). To clarify the mechanisms underlying the reduced ventricular remodeling in hypertensive heart diseases caused by bFGF, we examined the degree of interstitial fibrosis associated with alpha-smooth muscle actin expression and matrix metalloproteinase activity in hypertensive heart diseases.
  
  
  METHODS
  Dahl salt-sensitive rats were fed with a high-salt diet from 6 to 18 weeks of age and injected with a single dose of bFGF (100 microg) into the left myocardium at 15 weeks. Others were administered PBS without bFGF. Control age-matched Dahl salt-sensitive rats were fed with a low-salt diet.
  
  
  RESULTS
  Cardiac systolic function was well preserved and decompensation of heart failure was prevented at 18 weeks in the rats treated with bFGF at 15 weeks. The bFGF-treated rats had significantly fewer interstitial alpha-SMA-positive myofibroblasts and significantly decreased prolyl 4-hydroxylase expression. Increased matrix metalloproteinase-9 gelatinase activity correlated with the downregulation of transforming growth factor-beta1 by bFGF, suggesting that inhibited extracellular matrix deposition is associated with a decreased number of myofibroblasts induced by bFGF.
  
  
  CONCLUSIONS
  bFGF can inhibit the progression of ventricular remodeling by inhibiting interstitial fibrosis and promoting angiogenesis without decreasing blood pressure in hypertensive heart disease.
authors.affiliation: Department of Cardiovascular Medicine, Toho University Omori Medical Center, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Yoshikiyo
authors.initials: Y
authors.lastname: Akasaka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Namiki
authors.forename: Kinji
authors.initials: K
authors.lastname: Ito
authors.forename: Yukio
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Junichi
authors.initials: J
authors.lastname: Yamazaki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Ishii
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D016222:Fibroblast Growth Factor 2 / Q000502:physiology*; D005355:Fibrosis; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology*; D006973:Hypertension / Q000150:complications* / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology; D011393:Procollagen-Proline Dioxygenase / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D020257:Ventricular Remodeling / Q000502:physiology*
chemical_list: D000199:Actins; D016222:Fibroblast Growth Factor 2; D020780:Matrix Metalloproteinase 9; D011393:Procollagen-Proline Dioxygenase; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat