Thalidomide attenuates the development of fibrosis during post-infarction myocardial remodelling in rats.
Słowa kluczowe
Abstrakcyjny
BACKGROUND
Inflammation plays a pathogenic role in the development of heart failure (HF). The aim of this study was to examine the effect of treatment with the immunomodulating drug thalidomide in a rat model for post-myocardial infarction (MI) HF.
METHODS
Rats were subjected to MI by left coronary artery ligation or sham-operated. Seven days after surgical intervention rats were randomised to treatment with thalidomide or vehicle for 8 weeks.
RESULTS
Our main findings were: (i) thalidomide treatment did not affect cardiac function or the hypertrophic response, as determined by haemodynamic measurements and heart chamber weights, respectively. (ii) HF rats treated with thalidomide had a minor reduction in septum and relative wall thickness (p<0.05), indicating an anti-remodelling effect. (iii) Thalidomide appeared to have immunostimulatory effects on the myocardium as evident by increased MIP-1alpha gene expression (p<0.05). (iv) Treating HF rats with thalidomide reduced myocardial collagen content, as assessed by markedly decreased levels of hydroxyproline ( approximately 40% reduction; p<0.05), accompanied by lower TGF-beta(1) gene expression (p<0.05).
CONCLUSIONS
Although thalidomide had no effect on cardiac function, our results suggest that intervention with thalidomide may have beneficial effects in post-MI HF by attenuating collagen accumulation and development of myocardial fibrosis.
