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

• Published in: Transplantation proceedings Vol. 41; no. 6; pp. 2231 - 2233
• Main Authors: Batlle, M., Pérez-Villa, F., Lázaro, A., García-Pras, E., Vallejos, I., Sionis, A., Castel, M.A., Roig, E.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: Amsterdam Elsevier Inc 01.07.2009; Elsevier
• Subjects: Biological and medical sciences; Biopsy; Female; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gene Expression Regulation; Heart Failure - genetics; Heart Failure - pathology; Heart Transplantation - pathology; Humans; Male; Medical sciences; Middle Aged; Polymerase Chain Reaction; Reference Values; RNA - genetics; RNA, Messenger - genetics; Spectrophotometry; Surgery; Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases; Thrombospondin 1 - genetics; Tissue Donors; Tissue, organ and graft immunology; Transcription, Genetic; Transforming Growth Factor beta1 - genetics; Ventricular Remodeling - genetics; Heart; Medicine; Vascular remodeling; Treatment; Surgery; Graft; Transplantation; Circulatory system; Antiangiogenic agent; Gene expression; Thrombospondin 1
• ISSN: 0041-1345; 1873-2623; 1873-2623
• DOI: 10.1016/j.transproceed.2009.06.009

Thrombospondin-1 (TSP-1) is a potent inhibitor of angiogenesis and an activator of tissue transforming growth factor-β1 (TGF-β1). 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). We analyzed the expression of TSP-1 and TGF-β1 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 μg was retrotranscribed and mRNA expression levels were quantified by real-time polymerase chain reaction (PCR). 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-β1 (68.42 ± 4.36 vs 80.58 ± 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-β1 ( P = .001; R 2 = .2), and lower TSP-1 mRNA levels were observed with increasing left ventricular diameters. 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-β1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.