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.

Synthesis and Evaluation of 2‐Azetidinone and 1H‐Pyrrole‐2,5‐dione Derivatives as Cholesterol Absorption Inhibitors for Reducing Inflammation Response and Oxidative Stress

“…[12] Compelling evidence indicates that ezetimibe might attenuate atherosclerosis mediated by lowering cholesterol concentrations, protecting endothelial function, and decreasing inflammatory cytokines. [12] Compelling evidence indicates that ezetimibe might attenuate atherosclerosis mediated by lowering cholesterol concentrations, protecting endothelial function, and decreasing inflammatory cytokines.…”

“…During the formation and progression of atherosclerotic plaques, the inflammation response, oxidative stress, and endothelial damage appear to play vital roles. [12] Compelling evidence indicates that ezetimibe might attenuate atherosclerosis mediated by lowering cholesterol concentrations, protecting endothelial function, and decreasing inflammatory cytokines. [11] Then, we determined the protein level of inflammatory cytokine TNF-α in the Caco-2 cell lines for evaluating the anti-inflammatory activity of compound 14q.…”

“…[9] In addition to its lipid-lowering effect, it has also been shown to attenuate directly the platelet activation and the uPAR expression on endothelial cells, thereby providing further evidence of the possible pleiotropic therapeutic relevance of ezetimibe. [11] [12] The study of new CAI to improve the antihyperlipidemic effect and to give additional choice for the patients has already been acknowledged and recognized. [11] [12] The study of new CAI to improve the antihyperlipidemic effect and to give additional choice for the patients has already been acknowledged and recognized.…”

“…[10] Recent studies describe that ezetimibe alone indicated the same protective effect on the moderate atherosclerotic lesion compared to atorvastatin; the researchers believe that this anti-atherosclerotic effects of ezetimibe might result from lowering serum cholesterol, decreasing circulatory inflammatory cytokines, and inhibiting the macrophage accumulation in lesions. [11] [12] The study of new CAI to improve the antihyperlipidemic effect and to give additional choice for the patients has already been acknowledged and recognized.…”

5,2′‐dibromo‐2,4′,5′‐trihydroxydiphenylmethanone attenuates LPS‐induced inflammation and ROS production in EA.hy926 cells via HMBOX1 induction

“…Inflammation and oxidative stress play key roles in the progression of cardiovascular diseases, including AS . Therefore, the inhibition of inflammatory response and ROS production may be beneficial in preventing the development of AS .…”