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

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 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.

The predictive role of E/e′ on ischemic stroke and atrial fibrillation in Japanese patients without atrial fibrillation

“…Association between E/e 0 and atherothrombotic risks Diastolic dysfunction is presumably caused by cardiac fibrosis [14], which can be provoked by various atherothrombotic risk factors, including aging [15], hypertension [16], and diabetes mellitus [17,18]. Actually, in the present study, high E/e 0 was associated with various atherothrombotic risk factors.…”

The diagnostic value of plasma N-terminal connective tissue growth factor levels in children with heart failure

“…8 Connective tissue growth factor displays various biological effects including promoting cell proliferation, cell migration, extracellular matrix production, and angiogenesis. It has been confirmed that it plays an important role in the pathogenesis of various fibrotic disorders 9,10 including myocardial fibrosis, 11 and its plasma concentration also correlates with the severity of fibrotic diseases. 12 Notably, plasma connective tissue growth factor levels were increased in 52 adult patients with chronic heart failure and correlated with brain natriuretic peptide and NYHA functional class.…”

Immunohistochemical Detection of CTGF in the Human Eye

“…58 Besides local effects, systemic effects due to elevated plasma CTGF also need to be considered in TM-alterations. 59 This might represent a link for a systemic disease or syndrome acting on the TM as a locus minoris resistentiae that possibly leads to glaucoma. However, in this sense it should be mentioned that part of the aqueous humor leaves the eye through the non-conventional or alternative outflow pathway via the iris root and the sclera.…”