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Connective tissue growth factor and cardiac diastolic dysfunction: human data from the Taiwan diastolic heart failure
Cho-Kai Wu1, Yi-Chih Wang, Jen-Kuang Lee
1Division of Cardiology, Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, No. 7, Chung-Shan South Road, Taipei 100, and Yun-Lin, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.
Insights
Connective tissue growth factor (CTGF) is linked to diastolic heart failure severity and fibrosis. This study suggests CTGF may be an early diagnostic marker for diastolic dysfunction.
Area of Science:
- Cardiology
- Fibrosis Research
- Biomarker Discovery
Background:
- Connective tissue growth factor (CTGF) is an emerging marker for tissue fibrosis.
- Diastolic heart failure (DHF) is characterized by impaired cardiac relaxation and filling.
- Understanding the molecular mechanisms underlying DHF is crucial for early diagnosis and treatment.
Purpose of the Study:
- To investigate the association between CTGF and cardiac diastolic function.
- To explore the role of CTGF in myocardial fibrosis in the context of diastolic dysfunction.
- To validate CTGF as a potential early marker for DHF.
Main Methods:
- Utilized cellular and animal models of diastolic dysfunction (DD).
- Recruited 125 patients with DHF from the Taiwan Diastolic Heart Failure Registry.
- Assessed diastolic function using tissue Doppler imaging (E/e') and myocardial fibrosis via cardiac magnetic resonance imaging (CMRI).
Main Results:
- Plasma CTGF levels significantly correlated with the severity of DHF (E/e') and cardiac fibrosis in patients.
- In vitro, cardiomyocyte stretch increased CTGF secretion.
- Canine models showed increased myocardial CTGF expression and fibrosis following aortic banding, paralleling DD severity.
Conclusions:
- Plasma CTGF levels are associated with diastolic dysfunction severity and myocardial fibrosis in DHF patients.
- Myocardial stretch may be a key mechanism driving CTGF elevation.
- CTGF shows promise as an early diagnostic marker for DHF.
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 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.
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