Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress.
Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress.
复制标题
抑制表皮生长因子受体可通过减少炎症和氧化应激来减轻动脉粥样硬化
DOI：
10.1038/srep45917
复制
发表时间：
2017-04-04
影响因子：
4.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Wang L;Huang Z;Huang W;Chen X;Shan P;Zhong P;Khan Z;Wang J;Fang Q;Liang G;Wang Y
动脉粥样硬化是一种导致血管稳态丧失的进行性疾病，并引起纤维化、巨噬细胞泡沫细胞形成和平滑肌细胞增殖。最近的研究表明表皮生长因子受体（EGFR）参与血管病理生理和巨噬细胞氧化应激的调节。虽然氧化应激和炎症在动脉粥样硬化的发展中起着关键作用，但其潜在机制是复杂的，尚未完全了解。在本研究中，我们阐明了EGFR在高脂饮食诱导的载脂蛋白E基因敲除小鼠动脉粥样硬化中的作用。我们发现在动脉粥样硬化病变发展中EGFR磷酸化和活性增加。EGFR抑制可防止氧化应激、巨噬细胞浸润、促炎细胞因子诱导和病变内SMC增殖。我们进一步表明，EGFR通过Toll样受体4激活。Toll样受体4或EGFR通路的破坏导致炎症活动和泡沫细胞形成减少。这些研究表明EGFR在动脉粥样硬化的发病机制中起着关键作用，并提示EGFR可能是预防动脉粥样硬化发展的潜在治疗靶点。
Atherosclerosis is a progressive disease leading to loss of vascular homeostasis and entails fibrosis, macrophage foam cell formation, and smooth muscle cell proliferation. Recent studies have reported that epidermal growth factor receptor (EGFR) is involved vascular pathophysiology and in the regulation of oxidative stress in macrophages. Although, oxidative stress and inflammation play a critical role in the development of atherosclerosis, the underlying mechanisms are complex and not completely understood. In the present study, we have elucidated the role of EGFR in high-fat diet-induced atherosclerosis in apolipoprotein E null mice. We show increased EGFR phosphorylation and activity in atherosclerotic lesion development. EGFR inhibition prevented oxidative stress, macrophage infiltration, induction of pro-inflammatory cytokines, and SMC proliferation within the lesions. We further show that EGFR is activated through toll-like receptor 4. Disruption of toll-like receptor 4 or the EGFR pathway led to reduced inflammatory activity and foam cell formation. These studies provide evidence that EGFR plays a key role on the pathogenesis of atherosclerosis, and suggests that EGFR may be a potential therapeutic target in the prevention of atherosclerosis development.