Using Serum Transforming Growth Factor-β To Predict Myocardial Fibrosis
To the Editor:
We read with interest the timely review by Souders et al1 on the role of cardiac fibroblasts in the development of physiological and pathological cardiac conditions. Fibrosis has been linked to heart failure and arrhythmia and may explain the reasons for which contractile dysfunction has been the best predictor of ventricular arrhythmia and sudden cardiac death. Therefore, risk stratification for myocardial fibrosis may be an accurate method of predicting the emergence and course of both heart failure and arrhythmia. In our review of the literature, we found that transforming growth factor (TGF)-β has been shown to have a central role in stimulating fibroblasts and promoting their differentiation into myofibroblasts, which is a key step in the development of increased myocardial fibrosis in both infarcted and noninfarcted regions of the heart.2 Souders et al1 have cited a few studies that question the proliferating effect of TGF-β on cardiac fibroblasts. However, none of that cited research is an in vivo study, and as a matter of fact 2 of 4 of the studies3,4 cited by Souders et al support the proliferating effect of TGF-β on fibroblasts. One may suggest that this controversy on the exact role of TGF-β on fibroblasts in vivo, and some other potentially beneficial effect that TGF-β may have,5 will make it a fairly difficult therapeutic target for near future. However, to our knowledge, all studies agree on the association of an increased level of TGF-β with an increase in myocardial fibrosis. We therefore suggest that the serum level of TGF-β after myocardial infarction can be used as a risk stratification tool for predicting the development of myocardial fibrosis resulting in heart failure and ventricular arrhythmia. If this hypothesis is proven to be correct, it will greatly and positively affect the prevention and treatment of sudden cardiac death and heart failure.
Sources of Funding
Supported by NIH R01 HL085558, R01 HL073753, P01 HL058000 (to S.C.D.).