[Expression of connective tissue growth factor in cardiomyocyte of young rats with heart failure and benazepril intervention].
OBJECTIVE
Ventricular remodeling is an important pathologic progress in almost all end stage heart failure (HF), and it is characterized by ventricular thickening and cardiac fibrosis with poor prognosis. The connective tissue growth factor (CTGF), a new growth factor with multi-function, has an important role in fibrosis of tissue and organs. It has been demonstrated that angiotensin-converting enzyme inhibitor (ACEI) can prevent the development of cardiomyocyte from remodeling and improve cardiac function. Researchers try to test the hypothesis that cardiac function improvement attributable to ACEI is associated with inhibiting expression of CTGF in patients with HF. The aim of this study was to observe changes in CTGF expression in cardiomyocyte of young rats with HF and effect of benazepril on CTGF.


METHODS
The animal model of HF was established by constriction of abdominal aorta. Five weeks old rats were randomly divided into 3 groups after 6 weeks of operation: (1) HF group without treatment (n = 15); (2) HF group where rats were treated with benazepril (n = 15); (3) sham-operated group (n = 15) where rats were administered benazepril through direct gastric gavage. After 4 weeks of treatment, the high frequency ultrasound was performed. The expression of CTGF was detected by immunohistochemistry and semi-quantative reverse transcription-polymerase chain reaction.


RESULTS
Compared with the sham-operated group, left ventricular diastolic dimension (LVEDD), left ventricular systolic dimension (LVESD), interventricular septal thickness at end-diastole (IVSTd), interventricular septal thickness at end-systole (IVSTs), left ventricular posterior wall thickness at end-diastole (LVPWTd), left ventricular posterior wall thickness at end-systole (LVPWTs), left ventricular relative weight (LVRW), and right ventricular relative weight (RVRW) were all increased (P < 0.01), but ejection fraction (EF) and fractional shortening (FS) were decreased (P < 0.01). CTGF positive cells and expression of CTGF mRNA (0.609 +/- 0.065 vs 0.117 +/- 0.011, P < 0.01) were increased in HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were all decreased (P < 0.01), but FS and EF were increased (P < 0.01) in cases of HF treated with benazepril when compared with HF group without treatment. LVESD, IVSTd, IVSTs, LVPWTd, LVPWTs, LVRW and RVRW were higher (P < 0.01), EF and FS were lower (P < 0.01), CTGF positive cells and expression of CTGF mRNA were higher (P < 0.01) in HF group treated with benazepril than those of sham-operated group.


CONCLUSIONS
The expression of CTGF was increased in the cardiomyocyte of young rats with HF and benazepril could prevent left ventricular from remodeling partly and improve cardiac function by inhibiting the expression of CTGF in cardiomyocyte in cases of HF.
Zhang
Qin
Q
Department of Cardiology, Children's Hospital, Chongqing University of Medical Scienses, Chongqing 400014, China.
Yi
Qi-jian
QJ
Qian
Yong-ru
YR
Li
Rong
R
Deng
Bing
B
Wang
Qiao
Q
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D055513:Connective Tissue Growth Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D020257:Ventricular Remodeling / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D001552:Benzazepines; D012333:RNA, Messenger; D055513:Connective Tissue Growth Factor; C044946:benazepril