Sheng Li, Ye Ping, Liu Yong-Xue, Han Chun-Guang, Zhang Zhi-Yi
Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
Clin Exp Hypertens. 2008 Feb;30(2):109-19. doi: 10.1080/10641960801945840.
Agonists of the peroxisome proliferator-activated receptor alpha (PPARalpha) and gamma (gamma) exert anti-proliferative and anti-inflammatory effects that led to the testing of these drugs in experimental cardiac hypertrophy. However, the effect of PPAR beta/delta (beta/delta) agonists in hypertrophy is not yet known. In this paper, an experiment was conducted to explore whether PPARbeta/delta activation has an effect on cardiac hypertrophy. An in vitro cardiomyocyte hypertrophy from neonatal rats was induced with Angiotensin II (Ang II1micromol x L(-1)) stimulation. For the examination of PPAR beta/delta effect, the cultured rat cardiac myocytes were pretreated with GW0742 (10 micromol.L(-1)), an agonist of PPARbeta/delta, for 48h before Ang II stimulation. The following parameters in the cultured cells were determined: surface areas of myocytes were measured by the NIH Image Software; (3)H-leucine incorporation into myocytes was counted by liquid scintillometer; mRNA expression of PPARbeta/delta, ANP, BNP, MMP9, MMP2, and IL-1beta was detected by RT-PCR; PPARbeta/delta protein expression was evaluated with immunofluorescence staining; GW0742 could ameliorate Ang II-induced cardiomyocyte hypertrophy, as indicated by its inhibitory effects on the surface area of myocytes, and ANP and BNP mRNA expressions in myocytes and (3)H-leucine incorporation into myocytes. Meanwhile, GW0742 pretreatment exerted inhibition on mRNA expression augmentation of such cytokines as MMP9, MMP2, and IL-1beta in hypertrophic myocytes. In addition, the down-regulated expression of PPARbeta/delta mRNA and protein in hypertrophic myocytes was also significantly reversed by GW0742. We demonstrate for the first time that GW0742 exerts a beneficial effect on Ang II-induced cardiac hypertrophy and the relation to inflammation response.
过氧化物酶体增殖物激活受体α（PPARα）和γ（γ）激动剂具有抗增殖和抗炎作用，这使得这些药物在实验性心肌肥大中得到了测试。然而，PPARβ/δ（β/δ）激动剂在肥大中的作用尚不清楚。在本文中，进行了一项实验以探讨PPARβ/δ激活是否对心肌肥大有影响。用血管紧张素II（Ang II 1μmol·L⁻¹）刺激诱导新生大鼠体外心肌细胞肥大。为了检测PPARβ/δ的作用，在Ang II刺激前48小时，用PPARβ/δ激动剂GW0742（10μmol·L⁻¹）预处理培养的大鼠心肌细胞。测定培养细胞中的以下参数：用NIH图像软件测量心肌细胞的表面积；用液体闪烁计数器计数（³H）-亮氨酸掺入心肌细胞的量；通过RT-PCR检测PPARβ/δ、心房钠尿肽（ANP）、脑钠肽（BNP）、基质金属蛋白酶9（MMP9）、基质金属蛋白酶2（MMP2）和白细胞介素-1β（IL-1β）的mRNA表达；用免疫荧光染色评估PPARβ/δ蛋白表达。GW0742可以改善Ang II诱导的心肌细胞肥大，这表现为其对心肌细胞表面积、心肌细胞中ANP和BNP mRNA表达以及（³H）-亮氨酸掺入心肌细胞的抑制作用。同时，GW0742预处理对肥大心肌细胞中MMP9、MMP2和IL-1β等细胞因子的mRNA表达增加有抑制作用。此外，GW0742还显著逆转了肥大心肌细胞中PPARβ/δ mRNA和蛋白表达的下调。我们首次证明GW0742对Ang II诱导的心肌肥大具有有益作用，并与炎症反应相关。
