Activation of PPARgamma by pioglitazone does not attenuate left ventricular hypertrophy following aortic banding in rats.
Sustained left ventricular hypertrophy (LVH) accelerates cardiac dysfunction and heart failure. Previous reports have suggested that activation of the peroxisome proliferator-activated receptor gamma (PPARgamma)-dependent pathway is involved in development of cardiac hypertrophy. Thiazolidinediones (TZDs) such as pioglitazone activate PPARgamma and are clinically used as antidiabetics. Given inconsistent reports regarding effects of TZDs on LVH, we examined in the present study the influence of pioglitazone on LVH in a rat model of aortic banding. Aortic banding was induced in rats by clipping the ascending aorta. Animals received pioglitazone (3 mg/kg/day) or placebo. Echocardiographic, hemodynamic, histological, and biochemical measurements were performed after 2 and 4 weeks. Pressure gradient was comparable between pioglitazone- and placebo-treated animals after 2 and 4 weeks. Left ventricular function was not different between the groups. In sham as well as in banded animals, LV/body weight ratio was increased in pioglitazone- as compared to placebo-treated animals after 2 and 4 weeks. Furthermore, an increase in myocyte size and atrial natriuretic factor was observed in pioglitazone- compared to placebo-treated animals 4 weeks after aortic banding as well. The results of this study demonstrate that activation of PPARgamma via pioglitazone does not protect the myocardium from pressure overload-induced LVH in a rat model of aortic banding. The findings rather indicate a pro-hypertrophic effect of pioglitazone treatment after aortic banding.
Weiss
Celine S
CS
Department of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg Germany.
Hagenmüller
Marco
M
Pichler
Martina
M
Münz
Sebastian
S
Ochs
Marco
M
Buss
Sebastian J
SJ
Bekeredjian
Raffi
R
Katus
Hugo A
HA
Hardt
Stefan E
SE
D000818:Animals; D001013:Aorta, Thoracic / Q000601:surgery; D009320:Atrial Natriuretic Factor / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004452:Echocardiography; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000503:physiopathology*; D007004:Hypoglycemic Agents / Q000494:pharmacology* / Q000633:toxicity; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000187:drug effects* / Q000378:metabolism; D000077205:Pioglitazone; D051381:Rats; D017208:Rats, Wistar; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000633:toxicity; D016277:Ventricular Function, Left / Q000187:drug effects
D007004:Hypoglycemic Agents; D047495:PPAR gamma; D045162:Thiazolidinediones; D009320:Atrial Natriuretic Factor; D000077205:Pioglitazone