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Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity.

机译:柯萨奇病毒诱发的小鼠心肌炎:用于研究免疫毒性的自身免疫疾病模型。

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摘要

Excellent animal models are available for virus-induced and autoimmune heart disease that are remarkably similar to human disease. Developing good animal models for heart disease is crucial because cardiovascular disease is now the leading cause of death in the United States and is estimated to be the leading cause of death in the world by the year 2020. A significant proportion of heart disease in Western populations is associated with inflammation. Myocarditis, or inflammation of the heart muscle, is the major cause of sudden death in young adults. Although most individuals recover from acute myocarditis, genetically susceptible individuals may go on to develop chronic myocarditis and dilated cardiomyopathy (DCM) resulting in congestive heart failure. In this article, we describe a model of autoimmune myocarditis and DCM induced by inoculation with heart-passaged coxsackievirus B3 (CVB3). Intraperitoneal inoculation of susceptible mice with CVB3 induces acute cardiac inflammation from days 7 to 14 postinfection (pi) that progresses to chronic myocarditis and DCM from day 28 to at least 56 pi. The model of CVB3-induced myocarditis presented here allows dissection of the contribution of viral infection and xenobiotics on immune dysregulation and inflammation in the heart. An improved understanding of the interaction between environmental exposures and the development of heart disease represents a clear challenge for immunotoxicologists.
机译:优秀的动物模型可用于病毒诱发的和自身免疫性心脏病,与人类疾病极为相似。开发良好的心脏病动物模型至关重要,因为心血管疾病现已成为美国的主要死亡原因,并且据估计到2020年将成为世界上主要的死亡原因。西方人群中有相当比例的心脏病与炎症有关。心肌炎或心肌炎是年轻人突然死亡的主要原因。尽管大多数人都可以从急性心肌炎中恢复过来,但遗传易感者可能会继续发展为慢性心肌炎和扩张型心肌病(DCM),从而导致充血性心力衰竭。在本文中,我们描述了一种由心脏传播的柯萨奇病毒B3(CVB3)接种引起的自身免疫性心肌炎和DCM模型。易感小鼠的腹膜内接种CVB3会在感染后第7至14天(pi)引发急性心脏炎症,从感染后第28天至至少56 pi逐渐发展为慢性心肌炎和DCM。此处介绍的CVB3诱导的心肌炎模型可以解剖病毒感染和异源生物对心脏免疫功能失调和炎症的作用。对环境暴露与心脏病发展之间相互作用的更好理解对免疫毒理学家而言是一个明显的挑战。

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