NADPH Oxidase in Angiotensin II-induced Cardiac Fibrosis

描述（由申请人提供）：本提案探讨活性氧和NAD(P)H氧化酶在血管紧张素II诱导的心脏纤维化中的作用。NAD(P)H氧化酶是心血管细胞活性氧的主要来源。该实验室先前的研究表明，血管紧张素II在体外刺激活性氧的产生，并上调NAD(P)H在心脏纤维化病理生理中的表达。成纤维细胞向肌成纤维细胞的转化是心脏纤维化的一个关键过程。本研究的主要目的是：1)确定NAD(P)H氧化酶是否介导血管紧张素II体外诱导成纤维细胞向肌成纤维细胞的转化；2)建立NAD(P)H氧化酶在血管紧张素II慢性输注引起的心肌肥大和纤维化小鼠模型中的作用。阐明心脏成纤维细胞在心脏纤维化过程中转化为肌成纤维细胞的机制，将有助于深入了解人类高血压心脏病的病理生理学，并使未来开发特异性的不良心肌重构抑制剂成为可能。

DESCRIPTION (provided by applicant): This proposal investigates the roles of reactive oxgyen species and NAD(P)H oxidases in cardiac fibrosis induced by angiotensin II. NAD(P)H oxidases are the major sources of reactive oxygen species in cardiovascular cells. Previous work in this laboratory has shown that angiotensin II stimulates in vitro the production of reactive oxygen species and upregulates NAD(P)H expression in the pathophysiology of cardiac fibrosis. The transformation of fibroblasts to myofibroblasts represents a key process in cardiac fibrosis. This proposal addresses the following specific aims: 1) Determine whether an NAD(P)H oxidase mediates the transformation of fibroblasts into myofibroblasts by angiotensin II in vitro, and 2) Establish the role of NAD(P)H oxidases in mouse models of cardiac hypertrophy and fibrosis produced by chronic infusion of angiotensin II. Elucidation of the mechanisms by which cardiac fibroblasts transform into myofibroblasts during cardiac fibrosis will provide insight into the pathophysiology of human hypertensive heart disease and enable future development of specific inhibitors of adverse myocardial remodeling.