Thalidomide attenuates the development of fibrosis during post-infarction myocardial remodelling in rats.
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.
Research Institute for Internal Medicine, Rikshospitalet University Hospital, University of Oslo, N-0027 Oslo, Norway. arne.yndestad@klinmed.uio.no
Arne
A
Yndestad
Leif Erik
LE
Vinge
Reidar
R
Bjørnerheim
Thor
T
Ueland
Jacob E
JE
Wang
Stig S
SS
Frøland
Håvard
H
Attramadal
Pål
P
Aukrust
Erik
E
Oie
D000818:Animals; D001794:Blood Pressure; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D005355:Fibrosis / Q000139:chemically induced / Q000473:pathology; D015870:Gene Expression; D006909:Hydroxyproline / Q000378:metabolism; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000009:adverse effects* / Q000494:pharmacology; D020257:Ventricular Remodeling / Q000187:drug effects*
D016207:Cytokines; D013792:Thalidomide; D006909:Hydroxyproline