disruption of nrf2, a key inducer of antioxidant defenses, attenuates apoe-mediated atherosclerosis in micenrf2中断,一个关键的诱导物的抗氧化防御系统,变弱apoe-mediated小鼠动脉粥样硬化.pdfVIP

Disruption of Nrf2, a Key Inducer of Antioxidant Defenses, Attenuates ApoE-Mediated Atherosclerosis in Mice 1 2 1 3 1 Thomas E. Sussan , Jonathan Jun , Rajesh Thimmulappa , Djahida Bedja , Maria Antero , Kathleen L. 3 2 1,2 Gabrielson , Vsevolod Y. Polotsky , Shyam Biswal * 1 Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America, 2 Division of Pulmonary and Critical Care Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America, 3 Department of Molecular and Comparative Pathobiology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, United States of America Abstract Background: Oxidative stress and inflammation are two critical factors that drive the formation of plaques in atherosclerosis. Nrf2 is a redox-sensitive transcription factor that upregulates a battery of antioxidative genes and cytoprotective enzymes that constitute the cellular response to oxidative stress. Our previous studies have shown that disruption of Nrf2 in mice (Nrf22/ 2) causes increased susceptibility to pulmonary emphysema, asthma and sepsis due to increased oxidative stress and inflammation. Here we have tested the hypothesis that disruption of Nrf2 in mice causes increased atherosclerosis. Principal Findings: To investigate the role of Nrf2 in the development of atherosclerosis, we crossed Nrf22/ 2 mice with apoliporotein E-deficient (ApoE 2/ 2) mice. ApoE 2/ 2 and ApoE 2/ 2 Nrf22/ 2 mice were