Basic fibroblast growth factor inhibits ventricular remodeling in Dahl salt-sensitive hypertensive rats.
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.
Suzuki
Takeya
T
Department of Cardiovascular Medicine, Toho University Omori Medical Center, Japan.
Akasaka
Yoshikiyo
Y
Namiki
Atsushi
A
Ito
Kinji
K
Ishikawa
Yukio
Y
Yamazaki
Junichi
J
Ishii
Toshiharu
T
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*
D000199:Actins; D016222:Fibroblast Growth Factor 2; D020780:Matrix Metalloproteinase 9; D011393:Procollagen-Proline Dioxygenase; D053773:Transforming Growth Factor beta1; C498862:Acta2 protein, rat