Pathogenesis of Experimental Autoimmune Myocarditis

当心脏不能提供足够的含氧血液供应时，就会发生心力衰竭。 外周组织的代谢需求。有大量失败的主要原因， 几乎所有这些都可能伴随着心肌炎症，这是一种“适应性”过程，可能 实际上弊大于利。对心脏抗原，特别是心肌肌球蛋白的自身免疫可能 在人类和实验动物的炎症性心脏病期间发生在广泛的 感染、缺血性损伤和心脏毒性药物治疗。一个强大的实验模型 自身免疫性心肌炎(EAM)是由易感病毒株免疫引起的 在完全弗氏佐剂中加入纯化肌球蛋白的小鼠。在过去的十年里，我们做了很多工作 为了描述EAM模型的特征，已知它是(I)至少最初由CD4+T细胞介导的，(Ii) 两个阶段，先是炎症期，然后是修复和纤维化阶段。我们最近的工作是 重点阐述了EAM发病的基本机制，重点阐述了EAM的预防和治疗 恢复外周免疫耐受联合血管紧张素转换酶治疗自身免疫性心肌炎 转化酶抑制。我们组建了一支在病理学方面具有专业知识的研究团队， EAM的遗传学、免疫学以及分子和细胞生物学，并建议继续我们的工作 具体目的如下：(一)阐明炎症和消退的分子发病机制 肌球蛋白诱导的EAM的各阶段，重点是这些过程的功能免疫学，(Ii)到 探讨EAM免疫应答的抗原特异性及外周血淋巴细胞的潜能 耐受性诱导治疗正在进行的疾病和(Iii)探讨肾素的作用 血管紧张素系统在EAM发病机制中的作用

Cardiac failure occurs when the heart is unable to deliver a sufficient supply of oxygenated blood to serve the metabolic needs of the peripheral tissues. There are a large number of primary causes of failure, virtually all of which may be accompanied by myocardial inflammation as an "adaptive" process that may actually do more harm than good. Autoimmunity to cardiac antigens, cardiac myosin in particular, may develop during inflammatory heart disease in humans and experimental animals after a wide range of infections, ischemic damage and cardiotoxic drug treatment. A powerful model of experimental autoimmune myocarditis (EAM) has been developed that is initiated by immunization of susceptible strains of mice with purified myosin in complete Freund's adjuvant. Much has been done during the past decade to characterize the EAM model and it is known to be (i) mediated, at least initially, by CD4+ T cells and (ii) biphasic, with a proinflammatory phase followed by a phase of repair and fibrosis. Our recent work has focused on the basic mechanisms of EAM pathogenesis with an emphasis on the prevention and treatment of autoimmune myocarditis by restoration of peripheral immune tolerance and byangiotensin converting enzyme inhibition. We have assembled a research team with expertise in the pathology, genetics, immunology, and molecular and cellular biology of EAM, and propose to continue our work with the following Specific Aims: (i) to elucidate the molecular pathogenesis of the inflammatory and resolution phases of myosin-induced EAM, with a focus on the functional immunology of these processes, (ii)to investigate the antigen specificities of the immune responses in EAM and the potential of peripheral tolerance induction for the treatment of ongoing disease and (iii)to explore the role of the renin angiotensin system in EAM pathogenesis.