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-beta1 (TGF-beta1). 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).


METHODS
We analyzed the expression of TSP-1 and TGF-beta1 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 microg 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-beta1 (68.42 +/- 4.36 vs 80.58 +/- 5.26 ng-equiv; P < .05). TSP-1 mRNA levels correlated positively with TGF-beta1 (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-beta1 mRNA levels were lower in failing hearts, which suggested that fibrogenesis takes place in earlier phases of HF.
Batlle
M
M
Institut Clínic del Tòrax, Hospital Clínic and Institut d'Investigacions Biomèdiques August Pi i Sunyer, Barcelona, Spain. mbatlle@clinic.ub.es
Pérez-Villa
F
F
Lázaro
A
A
García-Pras
E
E
Vallejos
I
I
Sionis
A
A
Castel
M A
MA
Roig
E
E
D001706:Biopsy; D005260:Female; D005786:Gene Expression Regulation; D006333:Heart Failure / Q000235:genetics* / Q000473:pathology; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012313:RNA / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D013053:Spectrophotometry; D019700:Thrombospondin 1 / Q000235:genetics*; D014019:Tissue Donors; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D020257:Ventricular Remodeling / Q000235:genetics*
D012333:RNA, Messenger; D019700:Thrombospondin 1; D053773:Transforming Growth Factor beta1; D012313:RNA