Connective tissue growth factor and cardiac diastolic dysfunction: Human data from the Taiwan Diastolic Heart Failure Registry and molecular basis by cellular and animal models

Cho Kai Wu, Yi Chih Wang, Jen Kuang Lee, Sheng Nan Chang, Mao Yuan Su, Huei Ming Yeh, Ming Jai Su, Jin Jer Chen, Fu Tien Chiang, Juey Jen Hwang, Jiunn Lee Lin, Chia Ti Tsai

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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 A total of 125 patients with a diagnosis of diastolic heart failure (DHF) were recruited from 1283 patients of the and results: Taiwan Diastolic Heart Failure Registry. The severity of DHF was determined by tissue Doppler 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.

Original languageEnglish
Pages (from-to)163-172
Number of pages10
JournalEuropean Journal of Heart Failure
Volume16
Issue number2
DOIs
Publication statusPublished - Jan 1 2014
Externally publishedYes

Keywords

  • Canine model
  • Connective tissue growth factor
  • Diastolic heart failure
  • Fibrosis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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    Wu, C. K., Wang, Y. C., Lee, J. K., Chang, S. N., Su, M. Y., Yeh, H. M., Su, M. J., Chen, J. J., Chiang, F. T., Hwang, J. J., Lin, J. L., & Tsai, C. T. (2014). Connective tissue growth factor and cardiac diastolic dysfunction: Human data from the Taiwan Diastolic Heart Failure Registry and molecular basis by cellular and animal models. European Journal of Heart Failure, 16(2), 163-172. https://doi.org/10.1002/ejhf.33