[The effect of valsartan and fluvastatin on the connective tissue growth factor expression in experimental diabetic cardiomyopathy].
OBJECTIVE
To investigate the effect of valsartan and fluvastatin on the expression of connective tissue growth factor in early diabetic cardiomyopathy.


METHODS
Forty male SD rats were randomly divided into five groups: normal control group, diabetic model (DM) group, DM + valsartan group (30 mg x kg(-1) x d(-1)), DM + fluvastatin group (4 mg x kg(-1) x d(-1) ) and DM + valsartan + fluvastatin group (valsartan 30 mg x kg(-1) x d(-1) + fluvastatin 4 mg x kg(-1) x d(-1)). After 12 weeks, miniature cardiac catheter was inserted into the left ventricle to conduct hemodynamic examination. Then myocardial tissue was collected and collagen content was detected with Van-Gieson staining. The levels of connective tissue growth factor (CTGF) mRNA expression in myocardium were determined using RT-PCR and Western blot was used to detect the protein expression of transforming growth factor (TGF) beta, CTGF, collagen I and III.


RESULTS
By the end of the experiment, left ventricular diastolic function was significantly decreased in the DM group in comparison with the control group (P < 0.05). As compared with the normal control group, myocardial collagen content was significantly increased 1.1 fold (P < 0.05), and the heart weight/body weight ratio was increased 37% in the DM group, but it was significantly reduced in the valsartan group and the fluvastatin group in comparison with the DM group (both P < 0.05). The mRNA expression of CTGF was significantly higher in the DM group than in the control group, but it was significantly lower in the valsartan group and fluvastatin group than that in the DM group (both P < 0.05). The values of protein expression of CTGF, TGFbeta, collagen I and III were all significantly higher in the DM group than those in the control group (all P < 0.05). The protein expression of CTGF, TGFbeta, collagen I and III in the valsartan group and fluvastatin group was all significantly lower than that in the DM group (P < 0.05). It was shown that treatment with valsartan or fluvastatin was effective for myocardial fibrosis in diabetic SD rats and valsartan combined with fluvastatin would be still better.


CONCLUSIONS
Valsartan and fluvastatin can reduce myocardial fibrosis, resulting in prevention of left ventricular remodeling and improvement of cardiac function in an experimental model of diabetic cardiomyopathy. The process was related to the inhibition of the overexpression of CTGF and TGFbeta and reduction in cardiac extracellular matrix collagen content. It is also shown that a better result may be obtained with the coadministration of the two drugs than using one alone.
Wang
Yong-Jian
YJ
Department of Cardiology, Sir Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Fu
Guo-Sheng
GS
Chen
Fang-Ming
FM
Wang
Hui
H
D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism*; D003238:Connective Tissue / Q000378:metabolism; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D013777:Tetrazoles; D055513:Connective Tissue Growth Factor; D000077340:Fluvastatin; D000068756:Valsartan; D014633:Valine