Department of Cardiology, Xinqiao Hospital, Third Military Medical University, Chongqing, China.
J Cardiovasc Pharmacol. 2012 Jun;59(6):500-6. doi: 10.1097/FJC.0b013e31824c853c.
Recent studies have shown that atorvastain has anti-inflammatory effect and can prevent cardiac hypertrophy. The development of cardiac hypertrophy and dysfunction is associated with an increase in cardiac glucose utilization. In this study, we investigated the effect of atorvastatin on glucose oxidation in tumor necrosis factor α (TNF-α)-stimulated cardiomyocytes (H9c2 cells) and the potential role of peroxisome proliferation-activated receptor coactivator 1α (PGC-1α) in this effect. Exposure of H9c2 cells to TNF-α inhibited the expressions of PGC-1α, pyruvate dehydrogenase kinase 4, and carnitine palmityl transferase 1 and induced a significant increase in glucose oxidation rate. However, the effects of TNF-α were significantly reversed by atorvastatin. Selective silence of PGC-1α in H9c2 cells resulted in the downregulation of pyruvate dehydrogenase kinase 4 and carnitine palmityl transferase 1 and further increased the TNF-α-induced glucose oxidation. Interestingly, the effect of atorvastatin on PGC-1α was almost abolished by mevalonate and partially by farnesol but not by geranylgeraniol. In conclusion, atorvastatin inhibits TNF-α-induced glucose oxidation through PGC-1α upregulation in cardiomyocytes, which might be associated with the regulation of isoprenoid metabolites.
最近的研究表明，阿托伐他汀具有抗炎作用，可预防心肌肥厚。心肌肥厚和功能障碍的发展与心脏葡萄糖利用率的增加有关。在这项研究中，我们研究了阿托伐他汀对肿瘤坏死因子 α（TNF-α）刺激的心肌细胞（H9c2 细胞）中葡萄糖氧化的影响，以及过氧化物酶体增殖物激活受体共激活因子 1α（PGC-1α）在该作用中的潜在作用。TNF-α 暴露抑制了 PGC-1α、丙酮酸脱氢酶激酶 4 和肉碱棕榈酰转移酶 1 的表达，并诱导葡萄糖氧化率显著增加。然而，阿托伐他汀显著逆转了 TNF-α 的作用。H9c2 细胞中 PGC-1α 的选择性沉默导致丙酮酸脱氢酶激酶 4 和肉碱棕榈酰转移酶 1 的下调，并进一步增加了 TNF-α 诱导的葡萄糖氧化。有趣的是，阿托伐他汀对 PGC-1α 的作用几乎被甲羟戊酸完全废除，被法呢醇部分废除，但不受香叶醇影响。总之，阿托伐他汀通过心肌细胞中 PGC-1α 的上调抑制 TNF-α 诱导的葡萄糖氧化，这可能与异戊二烯代谢物的调节有关。
