Telmisartan modulates mitochondrial function in vascular smooth muscle cells
Telmisartan modulates mitochondrial function in vascular smooth muscle cells
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DOI：
10.1038/hr.2012.199
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发表时间：
2013-05-01
影响因子：
5.4
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
--
作者：
Takeuchi, Kiyo;Yamamoto, Koichi;Rakugi, Hiromi
动脉粥样硬化的发展与线粒体功能紊乱有关，线粒体功能紊乱会损害有效的三磷酸腺苷（ATP）的产生，增加超氧化物的产生，并诱导血管平滑肌细胞（VSMCs）随后的凋亡。由于过氧化物酶体增殖体激活受体γ (PPAR γ)在线粒体代谢的调节中具有潜在的重要作用，我们研究了部分PPAR γ激动剂和血管紧张素受体阻滞剂替米沙坦对VSMC线粒体相关细胞反应的影响。在人VSMC中，替米沙坦增加ATP水平和线粒体复合物II、琥珀酸脱氢酶的激活，减少H2O2的释放，减弱H2O2诱导的细胞凋亡标志物caspase 3/7活性的增加。依泊沙坦是一种血管紧张素II受体阻滞剂，缺乏激活PPAR γ的能力，对VSMC中线粒体相关的细胞反应没有影响。对PPAR γ缺乏的VSMC的研究表明，替米沙坦对线粒体功能的影响在很大程度上与PPAR γ无关，尽管PPAR γ的存在可以调节替米沙坦对H2O2水平的影响。这些发现表明替米沙坦对VSMC的线粒体代谢有显著影响，这可能与心血管疾病的发病机制有关，而且不仅仅涉及血管紧张素受体阻断和PPAR γ的激活。
The development of atherosclerosis is associated with disturbances in mitochondrial function that impair effective adenosine triphosphate (ATP) production, increase generation of superoxide and induce subsequent apoptosis in vascular smooth muscle cells (VSMCs). As peroxisome proliferator-activated receptor gamma (PPAR gamma) has a potentially important role in the regulation of mitochondrial metabolism, we studied effects of the partial PPAR gamma agonist and angiotensin receptor blocker telmisartan, on mitochondria-related cellular responses in VSMC. In human VSMC, telmisartan increased ATP levels and activation of mitochondrial complex II, succinate dehydrogenase, reduced the release of H2O2 and attenuated H2O2-induced increases in caspase 3/7 activity, a marker of cellular apoptosis. Eprosartan, an angiotensin II receptor blocker that lacks the ability to activate PPAR gamma, had no effect on these mitochondria-related cellular responses in VSMC. Studies in PPAR gamma-deficient VSMC revealed that the effects of telmisartan on mitochondrial function were largely independent of PPAR gamma although the presence of PPAR gamma modulated effects of telmisartan on H2O2 levels. These findings demonstrate that telmisartan can have significant effects on mitochondrial metabolism in VSMC that are potentially relevant to the pathogenesis of cardiovascular disease and that involve more than just angiotensin receptor blockade and activation of PPAR gamma.