Department of Cardiology, University Hospital Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2010 Apr;381(4):285-95. doi: 10.1007/s00210-009-0488-7. Epub 2010 Jan 27.
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.
持续的左心室肥厚（LVH）加速了心脏功能障碍和心力衰竭。先前的报告表明，过氧化物酶体增殖物激活受体γ（PPARγ）依赖性途径的激活与心肌肥厚的发展有关。噻唑烷二酮类（TZDs），如吡格列酮，可激活 PPARγ，临床上被用作抗糖尿病药物。鉴于 TZDs 对 LVH 的影响存在不一致的报告，我们在本研究中检查了吡格列酮在主动脉缩窄大鼠模型中对 LVH 的影响。通过夹闭升主动脉在大鼠中诱导主动脉缩窄。动物接受吡格列酮（3mg/kg/天）或安慰剂治疗。在 2 和 4 周后进行超声心动图、血流动力学、组织学和生化测量。在 2 和 4 周后，吡格列酮和安慰剂治疗的动物之间的压力梯度相当。左心室功能在两组之间没有差异。在假手术和缩窄动物中，与安慰剂治疗的动物相比，吡格列酮治疗的动物在 2 和 4 周后 LV/体重比增加。此外，在主动脉缩窄后 4 周，与安慰剂治疗的动物相比，吡格列酮治疗的动物观察到心肌细胞大小和心房利钠因子增加。这项研究的结果表明，通过吡格列酮激活 PPARγ 并不能保护心肌免受主动脉缩窄大鼠模型中压力超负荷引起的 LVH。研究结果表明，在主动脉缩窄后，吡格列酮治疗具有促肥厚作用。
