Decreased Expression of Thrombospondin-1 in Failing Hearts May Favor Ventricular Remodeling

Background. Thrombospondin-1 (TSP-1.) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor-beta 1 (TGF-beta 1). Analyses using genetically modified mice suggested that TSP-1 may play a protective role to prevent infiltration and tissue remodeling responses after myocardial infarction. The expression levels of TSP-1 and their putative role in ventricular remodeling have not been determined in patients with heart failure (HF). Materials and Methods. We analyzed the expression of TSP-1 and TGF-beta 1 mRNA in myocardial biopsies from 34 subjects with end-stage HF undergoing heart transplantation and 13 healthy controls from heart donors. Among total RNA extracted from the left ventricle, 1 mu g was retrotranscribed and mRNA expression levels were quantified by real-time polymerase chain reaction (PCR). Results. The mean age of subjects was 54 +/- 2 years; mean ejection fraction, 21 +/- 5%; end-diastolic diameter and end-systolic diameter, 73 +/- 10 and 61 +/- 11 mm, respectively. TSP-1. mRNA expression in ventricular tissue from HF patients was lower (159.04 +/- 14.55 ng-equivalents [ng-equiv]) than in controls (234 +/- 30.66 ng-equiv; P < .05). Tissue from HF subjects also showed lower levels of TGF-beta 1 (68.42 +/- 4.36 vs 80.58 +/- 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-beta 1 (P = .001; R-2 = .2), and lower TSP-1 mRNA levels were observed with increasing left ventricular diameters. Conclusions. Patients with end-stage HF show decreased TSP-1 mRNA levels, which agrees with published results showing lower circulating TSP-1. Ventricular dilatation observed in these patients may be related to lower expression of TSP-1. Surprisingly, TGF-beta 1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.