Activation of PPARγ by pioglitazone does not attenuate left ventricular hypertrophy following aortic banding in rats

Abstract

Sustained left ventricular hypertrophy (LVH) accelerates cardiac dysfunction and heart failure. Previous reports have suggested
that activation of the peroxisome proliferator-activated receptor γ (PPARγ)-dependent pathway is involved in development of
cardiac hypertrophy. Thiazolidinediones (TZDs) such as pioglitazone activate PPARγ 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 (3mg/kg/day) or placebo. Echocardiographic, hemodynamic, histological, and biochemical measurements were performed
after 2 and 4weeks. Pressure gradient was comparable between pioglitazone- and placebo-treated animals after 2 and 4weeks.
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 4weeks. Furthermore, an increase in myocyte
size and atrial natriuretic factor was observed in pioglitazone- compared to placebo-treated animals 4weeks after aortic
banding as well. The results of this study demonstrate that activation of PPARγ 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.

KeywordsPioglitazone-PPARγ-Left ventricular hypertrophy-Cardiac remodeling-Aortic banding