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To investigate the effect of estrogen receptor a (ER-a) during the process of insulin induced atherosclerosis.
Eight-week-old Apoe/Lepr double knockout mice (n = 8) were randomly divided in two groups: control group (N) and insulin group (INS), vascular atherosclerotic plaques and ER-a, alpha smooth muscle actin (SM-a) expression levels were detected by hematoxylin-eosin (HE) staining and immunohistochemical analysis. Insulin was applied to intervene rat vascular smooth muscle cells (VSMCs), and the DNA methyltransferase 3a (DNMT3a) and ER-a expression levels were assessed by RT-PCR and Western blot. Furthermore, Wound-Healing Assay and flow cytometry was used to detect the effect of ER-a on the VSMC proliferation and migration.
Animal study revealed that the experimental mice showed atherosclerosis plaques and lower ER-a, SM-a expression than the control group. The cell assay showed significantly lower ER-a and higher DNMT3a gene and protein expression (P＜0.05) in the experimental group than in the control group, and 5-Aza-2′-deoxycytidine (5-Aza) can eliminate this difference. Wound-Healing Assay and flow cytometry shown ER-a might inhibit the proliferation and migration of VSMC.
ER-a has the effect of inhibiting proliferation and migration of VSMC. By up-regulating the expression of DNMT3a, Insulin tends to suppress the expression of ER-a, then inducing the formation of atherosclerosis.