It has been reported that cholesterol-lowing agents can ameliorate severity of myocarditis. However, the beneficial effect of the agents has been claimed to be independent of cholesterol reduction as there is no significant change in the plasma cholesterol level in myocarditis. In the present study, using experimental autoimmune myocarditis (EAM) rats as an animal model, we demonstrated that EAM induced elevation of cholesterol level and impaired cholesterol efflux capacity in the cardiac tissue. Moreover, serum high-density lipoprotein (HDL) content was reduced and HDL function associated protein Paraoxonase 1 (PON1) activity was decreased. Besides, the major structural protein within HDL, Apolipoprotein A1 (ApoA1) expression in the cardiac tissues was significantly reduced while the level of serum ApoA1 was not significantly altered. Importantly, cholesterol depleting agent methyl-β-cyclodextrin (MβCD) alleviated the development of EAM, as monitored by decreased ratio of heart weight to body weight (HW/BW), decreased infiltration of inflammatory cells and collagen deposition, improved cardiac function, reduced expression of apoptosis-related protein Bax, Fas, FasL and caspase-3 and increased level of anti-apoptotic protein Bcl-2. These results suggest that reduction of cholesterol level in cardiac tissue could suppress EAM-induced cardiac apoptosis through both intrinsic and extrinsic apoptotic pathways.

据报道，降胆固醇药可改善心肌炎的严重程度。然而，由于在心肌炎中血浆胆固醇水平没有显着变化，因此已声称该试剂的有益作用与胆固醇降低无关。在本研究中，使用实验性自身免疫性心肌炎（EAM）大鼠作为动物模型，我们证明了EAM会引起心脏组织中胆固醇水平升高和胆固醇外排能力受损。此外，降低了血清高密度脂蛋白（HDL）含量，降低了HDL功能相关蛋白对氧磷酶1（PON1）的活性。此外，HDL中的主要结构蛋白，载脂蛋白A1（ApoA1）在心脏组织中的表达显着降低，而血清ApoA1的水平没有明显改变。重要的，胆固醇减少剂甲基-β-环糊精（MβCD）减轻了EAM的发展，可通过降低心重与体重之比（HW / BW），减少炎性细胞浸润和胶原沉积，改善心脏功能，降低EGF的表达来监测凋亡相关蛋白Bax，Fas，FasL和caspase-3以及抗凋亡蛋白Bcl-2的水平升高。这些结果表明，降低心脏组织中的胆固醇水平可以通过内在和外在的凋亡途径抑制EAM诱导的心脏凋亡。降低凋亡相关蛋白Bax，Fas，FasL和caspase-3的表达，并提高抗凋亡蛋白Bcl-2的水平。这些结果表明，降低心脏组织中的胆固醇水平可以通过内在和外在的凋亡途径抑制EAM诱导的心脏凋亡。降低凋亡相关蛋白Bax，Fas，FasL和caspase-3的表达，并提高抗凋亡蛋白Bcl-2的水平。这些结果表明，降低心脏组织中的胆固醇水平可以通过内在和外在的凋亡途径抑制EAM诱导的心脏凋亡。