Atorvastatin 抑制氣球導致受傷模式下造成之myocardin過度表現老鼠頸動脈內膜肥厚

Atorvastatin Inhibits Balloon Injury-Induced Myocardin Expression and Carotid Intimal Hyperplasia in Adult Rat

背景和目的：Statin已知可有效抑制血管平滑肌肥大。Myocardin為一於血管平滑肌肥厚時增加表現之心臟調控基因。然而，現今對於頸動脈受傷模式下造成血管平滑肌肥厚時，statin對myocardin基因表現之影響所知仍有限。方法：為了瞭解statin 對myocardin表現及血管平滑肌肥厚之影響，成年之Sprague-Dawley 鼠頸動脈於氣球導致受傷2周後造成血管平滑肌肥厚。Atorvastatin（30毫克/ 公斤）之後每天投與或以myocardin之short interfering RNA（siRNA）使用嘗試抑制myocardin表現及頸動脈受傷模式下造成血管平滑肌肥厚。結果：Myocardin 蛋白及mRNA表現於頸動脈受傷模式下均上昇。而以atorvastatin 或myocardin siRNA皆有效減少myocardin蛋白或myocardin mRNA之表現。同時進一步回復因頸動脈受傷模式下造成血管平滑肌內膜增厚及血管腔室窄小。免疫組織化學標記亦可顯示smooth muscle α-actin及myocardin表現於頸動脈受傷後增加，而被atorvastatin或myocardin siRNA抑制。結論：Myocardin蛋白或myocardin mRNA表現於頸動脈受傷模式下造成血管平滑肌肥厚時增加，以atorvastatin或myocardin siRNA治療可回復myocardin 對此血管平滑肌肥厚之不正常調控。

Background and purpose: The use of statin has been documented to be effective to inhibit vascular smooth muscle cell (VSMC) hypertrophy. Myocardin, a cardiac regulated gene, is up-regulated in VSMC hypertrophy. However, the effect of statin on myocardin expression due to balloon injury-induced carotid intimal hyperplasia is little known. Methods: To evaluate the effect of statin on myocardin expression and VSMC hypertrophy, balloon injury to carotid artery of adult Sprague-Dawley rats was performed to induce VSMC hypertrophy. Atorvastatin (30 mg/kg) was given per day after surgery for 14 days. Results: Both myocardin mRNA and protein increased significantly after balloon injury to carotid artery, which was inhibited by either myocardin small interfering RNA (siRNA) or atorvastatin. Increased intimal areas and decreased lumen to intima ratios of carotid artery were noted after balloon injury, which was also inhibited by myocardin siRNA and atorvastation. Increased immunohistochemical labelings of myocardin and smooth muscle (SM) actin in the VSMCs of carotid artery were observed and atorvastatin or myocardin siRNA again reversed the labelings. Conclusions: Both myocardin protein and myocardin mRNA expressions were up-regulated in the rat model of balloon injury-induced VSMC hypertrophy. Treatment with atorvastatin or myocardin siRNA is associated with a reversal of abnormal regulation of myocardin in the hypertrophic VSMC of carotid artery.