title: Inhibition of epidermal growth factor receptor attenuates atherosclerosis via decreasing inflammation and oxidative stress.
abstract: 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.
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Lintao
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Cardiology, the First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Peiren
authors.initials: P
authors.lastname: Shan
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhong
authors.affiliation: Department of Pathology and Laboratory Medicine, Western University, London, ON N6A5C1, Canada.
authors.forename: Zia
authors.initials: Z
authors.lastname: Khan
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Jingying
authors.initials: J
authors.lastname: Wang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Qilu
authors.initials: Q
authors.lastname: Fang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D066246:ErbB Receptors / Q000235:genetics*; D005487:Foam Cells / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D008264:Macrophages; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress / Q000235:genetics; D058226:Plaque, Atherosclerotic / Q000473:pathology; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C541485:EGFR protein, mouse; D066246:ErbB Receptors