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Connective tissue growth factor and cardiac diastolic dysfunction: human data from the T aiwan D iastolic H eart F ailure R egistry and molecular basis by cellular and animal models
Author(s) -
Wu ChoKai,
Wang YiChih,
Lee JenKuang,
Chang ShengNan,
Su MaoYuan,
Yeh HueiMing,
Su MingJai,
Chen JinJer,
Chiang FuTien,
Hwang JueyJen,
Lin JiunnLee,
Tsai ChiaTi
Publication year - 2014
Publication title -
european journal of heart failure
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.149
H-Index - 133
eISSN - 1879-0844
pISSN - 1388-9842
DOI - 10.1002/ejhf.33
Subject(s) - ctgf , connective tissue , medicine , cardiac fibrosis , fibrosis , growth factor , diastole , myocardial fibrosis , heart failure , endocrinology , pathology , cardiology , blood pressure , receptor
Aims Connective tissue growth factor ( CTGF ) is an emerging marker for tissue fibrosis. We investigated the association between CTGF and cardiac diastolic function using cellular and animal models and clinical human data. Methods and results A total of 125 patients with a diagnosis of diastolic heart failure ( DHF ) were recruited from 1283 patients of the T aiwan D iastolic H eart F ailure R egistry. The severity of DHF was determined by tissue D oppler imaging (E/e′). Cardiac magnetic resonance imaging ( CMRI ) was used to evaluate myocardial fibrosis in some of the patients ( n = 25). Stretch of cardiomyocytes on a flexible membrane base serves as a cellular phenotype of cardiac diastolic dysfunction ( DD ). A canine model of DD was induced by aortic banding. A significant correlation was found between plasma CTGF and E/e′ in DHF patients. The severity of cardiac fibrosis evaluated by CMRI also correlated with CTGF . In the cell model, stretch increased secretion of CTGF from cardiomyocytes. In the canine model, myocardial tissue CTGF expression and fibrosis significantly increased after 2 weeks of aortic banding. Notably, the expression of CTGF paralleled the severity of LV DD ( r = 0.40, P < 0.001 for E/e') and haemodynamic changes ( r = 0.80, P < 0.001). After adjusting for confounding factors, CTGF levels still correlated with diastolic parameters in both human and canine models (human plasma CTGF , P < 0.001; canine tissue CTGF , P = 0.04). Conclusion Plasma CTGF level correlated with the severity of DD and tissue fibrosis in DHF patients. The mechanism may be through myocardial stretch. Our study indicated that CTGF may serve as an early marker for DHF .