[Effect of valsartan on Tribble 3 gene expression in rats with experimental diabetic cardiomyopathy].
OBJECTIVE
Tribbles, a protein family controlling mitogen-activated protein kinase cascades, might contribute to the remodeling process in dilated cardiomyopathy. We investigated the gene expression of Tribble 3 (TRB(3)), cardiac function and collagen changes in rats with diabetic cardiomyopathy (DCM) and the modulating effects of valsartan on them.


METHODS
Male Wistar rats were fed with high cholesterol diet throughout the study period, streptozocin (30 mg/kg, i.p) was given at the 28th day, valsartan (30 mg.kg(-1).d(-1), n = 13) or placebo (n = 11) was administered at the 35th day to rats with fasting blood glucose > or = 11.1 mmol/L per gavage for another 12 weeks. Control rats (n = 8) were fed with regular chow. Fasting blood glucose was monitored throughout the study, left ventricular function was determined by echocardiography, myocardial collagen content quantified after Masson-staining and myocardial mRNA expression of TRB(3) detected by quantification real-time RT-PCR at the end of study.


RESULTS
Cardiac function was significantly improved (EF: 74% +/- 10% vs. 66% +/- 7%, P < 0.05), myocardial collagen content decreased (13.23 +/- 3.14 vs. 16.92 +/- 3.18, P < 0.05) in rats with DCM treated with valsartan. Moreover, TRB(3) mRNA was significantly increased in rats with DCM compared to control rats (0.0198 +/- 0.0082 vs. 0.1108 +/- 0.0933, P < 0.05) and the increase could be significantly attenuated by valsartan (0.0367 +/- 0.0234, P < 0.05 vs. DCM). A significant positive correlation was observed between myocardial TRB(3) mRNA and myocardial collagen content (r = 0.67, P < 0.05) and between TRB(3) mRNA and fasting blood glucose (r = 0.69, P < 0.05) in rats with DCM.


CONCLUSIONS
Our results show for the first time that myocardial TRB(3) mRNA is upregulated in rats with DCM and which could be down-regulated by valsartan.
Zhang
Wei
W
Department of Cardiology, Qilu Hospital of Shandong University, Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education and Public Health, Jinan 250012, China.
Zhong
Ming
M
Tang
Meng-xiong
MX
Ma
Xiao
X
Miao
Ya
Y
Sun
Hui
H
Zhang
Yun
Y
D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000378:metabolism* / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental; D015870:Gene Expression; D008297:Male; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
D012333:RNA, Messenger; D013777:Tetrazoles; C502443:Trib3 protein, rat; D000068756:Valsartan; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D014633:Valine