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 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.

In Vivo and In Vitro Protective Effects of Pentamethylquercetin on Cardiac Hypertrophy

“…Clinical studies demonstrated that left ventricular hypertrophy, independent of the underlying hypertrophic stimulus, is a major risk factor for cardiac ischemia, arrhythmia, and sudden death [2,3]. Pathological alterations of cardiac hypertrophy, including left ventricle wall thickness, myocyte size increment, myocyte disarray, fibrosis, and protein synthesis up-regulation, are preceded and accompanied by the reinduction of a fetal gene program [4,5].…”

“…Primary remodeling is a compensatory reaction to sustain normal cardiac function. However, further maladaption results in progressive, decompensated heart failure and sudden death [1,2,[4][5][6]. Thus, searching for novel therapeutic targets in cardiac hypertrophy, aiming at providing the opportunities to prevent, or even reverse its progression rather than treating the established cardiomyopathy or heart failure, has currently become a new strategy [2].…”

Chronic Akt blockade aggravates pathological hypertrophy and inhibits physiological hypertrophy

“…Animals were anesthetized as described above. After orotracheal intubation and ventilation, the thorax was opened left parasternally, and AB was induced by clipping the aorta ascendens, as previously described in detail (1,26,44).…”

Protective effects of tannic acid on pressure overload-induced cardiac hypertrophy and underlying mechanisms in rats

“…Cardiac hypertrophy is a growth in the mass of the contractile and ancillary proteins of the heart above what is considered normal for the given stage of its maturational increase . In its initial stages, cardiac hypertrophy is a compensatory reaction to sustained, regular cardiac function, but in later stages, maladaption results in progressive, pathological cardiac hypertrophy, which eventually leads to heart failure . Hence, searching for new therapeutic objectives in cardiac hypertrophy, which are aimed at stopping or reversing its progression rather than treating the vested cardiomyopathy or heart failure, is the present strategy .…”

“…[4][5][6][7] Hence, searching for new therapeutic objectives in cardiac hypertrophy, which are aimed at stopping or reversing its progression rather than treating the vested cardiomyopathy or heart failure, is the present strategy. [7] Epidemiological studies have indicated that the French population has lower mortality from cardiac disease, despite consuming a high-cholesterol diet, when compared with other developed countries. This French paradox was may be attributed to the high consumption of French red wine, which supports the hypothesis of that red wine exerts specific cardioprotective effects.…”