Cigarette smoke–mediated oxidative stress, shear stress, and endothelial dysfunction: role of VEGFR2
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説明
<jats:p>Vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2), a tyrosine kinase receptor, is activated by VEGF and fluid shear stress (FSS), and its downstream signaling is important in regulation of endothelial functions, such as cell migration, endothelium‐dependent relaxation, and angiogenesis. Inhibition of VEGFR2 augments cigarette smoke (CS)‐induced oxidative stress and inflammatory responses leading to endothelial dysfunction. CS‐derived reactive oxygen/nitrogen species interact with VEGFR2, causing posttranslational modifications that render VEGFR2 inactive for downstream signaling, resulting in endothelial dysfunction. CS‐mediated oxidants/carbonyl stress decreases SIRT1 levels and causes eNOS acetylation, which has ramifications in endothelial dysfunction. CS also affects endothelial cell survival pathway by disrupting VEGF‐ and FSS‐mediated VEGFR2/PI3‐kinase signaling, leading to decreased Akt phosphorylation and eNOS acetylation. We describe here the mechanisms whereby CS alters VEGF‐ and FSS‐mediated VEGFR2‐eNOS signaling, which may have implications for understanding the pathogenesis of pulmonary and cardiovascular diseases.</jats:p>
収録刊行物
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- Annals of the New York Academy of Sciences
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Annals of the New York Academy of Sciences 1203 (1), 66-72, 2010-08
Wiley