Disruption of natural healing process in autoimmune myocarditis and progression to dilated cardiomyopathy

(1)心肌炎标志物初发时sFas和sFasL水平升高是预测急性心肌炎预后的良好血清学指标。MCP-1可能在人急性心肌炎和大鼠实验性自身免疫性心肌炎(EAM)的发病机制中发挥重要作用。血清IL-10水平可作为评价心肌结节病病情活动性的指标。(2)心肌病的治疗小剂量卡维地洛对大鼠扩张型心肌病有一定的治疗作用。奎那普利能明显缩小实验性自身免疫性心肌炎慢性期的心肌纤维化面积。比索洛尔通过减少EAM患者猝死而独立提高存活率，这与其对左心功能的影响无关。应用抗CD_2单抗预防诱导期T细胞耗尽所致的EAM；(3)体内电穿孔基因转移EAM的基因治疗是一种…(4)EAMα-心肌肌球蛋白基因表达在第14天下降26倍，β-心肌肌球蛋白基因表达在第14天增加3.9倍，心钠素和脑钠素在第21天和第14天分别增加48倍和6.4倍。但仅在第14天和第21天检测到醛固酮合成酶。IL-2、IL-10、干扰素-γ和单核细胞趋化蛋白-1在第14天、第398天、43天和第14天分别增加了9倍和142倍。在第21天，3型胶原、1型胶原和纤维连接蛋白分别增加35倍、1.7倍和45倍。有趣的是，骨桥蛋白在第14天时增加了4542倍，是所有基因中最高的。EAM中心肌肌球蛋白和NP的亚型发生了显著的变化。RAA和ET的表达在EAM的时程中有不同程度的变化。细胞因子、趋化因子和细胞外基质大量增加，尤其是早期EAM中大量表达骨桥蛋白。较少

(1) Marker in myocarditisElevation of sFas and sFasL levels at initial presentation appear to be a good serological marker to predict the prognosis of acute myocarditis. MCP-1 may play an important role in the pathogenesis of human acute myocarditis as well as in the progression of rat Experimental autoimmune myocarditis (EAM). Serum IL-10 levels may play a role m evaluation of the disease activity in patients with cardiac sarcoidosis.(2) Therapy for myocarditisA low dose of carvedilol has beneficial effects on rat dilated cardiomyopathy The area of myocardial fibrosis in chronic phase of Experimental autoimmune myocarditis was markedly reduced by quinapril. Bisoprolol improved survival independently, of its effect on left ventricular function by reducing sudden death in EAM. The prevention of EAM by administering the anti-CD 2 monoclonal antibody resulted from T cell depletion during theinduction phase,(3) Gene therapy for EAMGene transfer into muscle by electroporation in vivo is an … More effective means of delivery of IL-10, INFγ receptor-IgG, secretary leukocyte protease inhibitor-IgG and CTLA4-IgG for the treatment of autoimmune myocarditis.(4) Time Course of Gene Expression in EAMα-cardiac myosin showed a 26-fold decrease and β-cardiac myosm a 3.9-fold increase at day 14. ANP and BNP increased 48- and 6.4-fold respectively at day 21 and 14. AT1 receptor, ACE and ET1 increased 22- at day 21, 6.3- at day 21 and 17-fold, respectively at day 14. Aldosterone receptor decreased 2.2-fold at day 14, but aldsterone synthethase was detected only at day 14 and 21. Interleukin (IL) -2, IL-10, interferon-γ and monocyte chemoattractant protein-1 increased 9.1- at day 14, 398- at day 21, 43- at day 14 and 142-fold at day 14, respectively. Collagen type 3, Collagen type 1 and fibronectin increased 35-, 1.7- and 45- fold at day 21. Interestingly, osteopontin showed a 4542-fold increase and it was the higtest mRNA of all at day 14.Isoform of cardiac myosin and NP are dramatically changed in EAM. RAA and ET expressions are changed diversely in EAM time course. Cytokine, chemokine and ECM greatly increase and, especially, large numbers of osteopontin mRNA are expressed in early EAM. Less