Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.
Atorvastatin Improves Ventricular Remodeling after Myocardial Infarction by Interfering with Collagen Metabolism.
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DOI：
10.1371/journal.pone.0166845
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Petrucci O
中科院分区：
文献类型：
--
作者：
Reichert K;Pereira do Carmo HR;Galluce Torina A;Diógenes de Carvalho D;Carvalho Sposito A;de Souza Vilarinho KA;da Mota Silveira-Filho L;Martins de Oliveira PP;Petrucci O
调节心室重塑的治疗策略在急性心肌梗死（MI）后可能有用。特别是，他汀类药物可能对参与胶原代谢的分子途径产生影响。本研究的目的是确定阿托伐他汀治疗 4 周是否会导致 MI 大鼠模型中胶原代谢和心室重塑的变化。本研究使用雄性 Wistar 大鼠。通过结扎左冠状动脉前降支（LAD）在大鼠中诱导心肌梗死。根据治疗，动物被随机分为三组：不进行LAD结扎的假手术（假手术组，n = 14），LAD结扎后接10mg阿托伐他汀/公斤/天，持续4周（阿托伐他汀组，n = 24），或LAD结扎后接生理盐水溶液4周（对照组，n = 27）。 4周后，通过压力-容量导管获得血流动力学特征。取出心脏，并对左心室进行纤维化程度和胶原沉积以及肌细胞横截面积的组织学分析。还评估了参与胶原代谢和炎症的介质的表达水平。与对照组相比，阿托伐他汀组的舒张末期容积、纤维化含量和肌细胞横截面积显着减少。阿托伐他汀调节远端梗塞区域中与胶原代谢相关的蛋白质的表达水平，包括 MMP1、TIMP1、COL I、PCPE 和 SPARC。 TLR4、IL-1 和 NF-kB p50 表达水平较低表明阿托伐他汀具有抗炎作用。阿托伐他汀治疗 4 周能够减轻大鼠心肌梗死后的心室功能障碍、纤维化和左心室肥厚，部分原因可能是通过对胶原代谢和炎症的影响。阿托伐他汀可能有助于限制心肌缺血事件后的心室重构。
Therapeutic strategies that modulate ventricular remodeling can be useful after acute myocardial infarction (MI). In particular, statins may exert effects on molecular pathways involved in collagen metabolism. The aim of this study was to determine whether treatment with atorvastatin for 4 weeks would lead to changes in collagen metabolism and ventricular remodeling in a rat model of MI. Male Wistar rats were used in this study. MI was induced in rats by ligation of the left anterior descending coronary artery (LAD). Animals were randomized into three groups, according to treatment: sham surgery without LAD ligation (sham group, n = 14), LAD ligation followed by 10mg atorvastatin/kg/day for 4 weeks (atorvastatin group, n = 24), or LAD ligation followed by saline solution for 4 weeks (control group, n = 27). After 4 weeks, hemodynamic characteristics were obtained by a pressure-volume catheter. Hearts were removed, and the left ventricles were subjected to histologic analysis of the extents of fibrosis and collagen deposition, as well as the myocyte cross-sectional area. Expression levels of mediators involved in collagen metabolism and inflammation were also assessed. End-diastolic volume, fibrotic content, and myocyte cross-sectional area were significantly reduced in the atorvastatin compared to the control group. Atorvastatin modulated expression levels of proteins related to collagen metabolism, including MMP1, TIMP1, COL I, PCPE, and SPARC, in remote infarct regions. Atorvastatin had anti-inflammatory effects, as indicated by lower expression levels of TLR4, IL-1, and NF-kB p50. Treatment with atorvastatin for 4 weeks was able to attenuate ventricular dysfunction, fibrosis, and left ventricular hypertrophy after MI in rats, perhaps in part through effects on collagen metabolism and inflammation. Atorvastatin may be useful for limiting ventricular remodeling after myocardial ischemic events.
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