The Effect And Mechanism Of Homer In Atherosclerosis

Background Atherosclerosis is a systemic arterial system category of violations diseases, mainly involving large and medium arteries, showed intimal thickening, foam cell appears, the formation of arterial plaque, thrombus formation, rupture of unstable plaque, cause coronary artery disease, acute coronary syndrome,troke and other cardiovascular diseases. Epidemiological studies have demonstrated that genetic factors, high blood pressure, high cholesterol, high blood sugar, smoking, lack of physical exercise etc. is the risk of coronary heart disease. The pathogenesis of lipoprotein oxidation and inflammation is an important mechanism for the pathogenesis of atherosclerosis. Studies have found that ApoE double knockout mice for atherosclerosis model, the two-dimensional electrophoresis mass spectrometry found that Homer2expression increased. Cultured vascular smooth muscle cells with calcification, Homer2gene expression increased. IL-13stimulated monocytes leads to atherosclerosis-related genes increase, which Homer2expression increased. In vascular aneurysm, Homer2a expression also increased, suggesting that Homer protein involved with the development of atherosclerosis, specially Homer2protein. This study intends to build cell models of atherosclerosis, oxidized LDL stimulate vascular smooth muscle cells, studied the relevance of Homer with cells apoptosis, proliferation, by inhibit or increase the expression Homer2, study the role of Homer2in the development of atherosclerosis, study the expression and the role of Homer2in mouse model with atherosclerosis, and human coronary heart disease, serum collected, study the relationship between levels of plasma lipoprotein and the expression of Homer protein. Study the role of Homer in the arteries and the development mechanism of atherosclerosis.METHODS Primary vascular smooth muscle cells, take3-8generation cells, we identify different subtypes of Homer proteins express in vascular smooth muscle cells by RT-PCR, Western blot and immunofluorescence; we add different concentrations of oxidized low-density lipoprotein in VSMCs construct cells models of atherosclerosis, by fluorescence quantitative PCR, Western blot study,We found different concentrations of oxidized LDL stimulation VSMCs, the expression of three isoforms of Homer related with the proliferation and apoptosis of VSMCs, while overexpression or inhibit the expression of Homer2of VSMCs, with apoptosis and proliferation different. High fat fed mice for construction animal models of atherosclerosis Immunohistochemical study the homer2expression in thoracoabdominal aortic site, and the correlation with apoptosis. Collection sera from coronary heart disease patient, studied relevance between the expression of Homer protein and the concentration of lipid.Results The primary vascular smooth muscle cells was isolated, by RT-PCR, Western blot and immunofluorescence,We found Homerl, Homer2, Homer3expressed, which Homer2with lower expression, gene and protein level results was consistent. Oxidized LDL stimulated vascular smooth muscle cells build a cell model of atherosclerosis, with concentration increase, Homer2expression increased, Homerl and Homer3did not change significantly, with apoptosis increase but no significant increase in cell proliferation. Vascular smooth muscle cells transfected with full-length construct in Homer2, increased apoptosis, siRNA Homer2with less apoptosis. Atherosclerosis in mouse model, HE staining found wall plaque formation, projecting into the lumen, immunohistochemistry showed that compared with normal blood vessels, atherosclerosis model Homer2expression increased. Coronary heart disease in human serum found that the expression level of Homer2and the expression of lipid level have some relevance.Conclusions In cellular, animal and human atherosclerosis model,We found Homer2have some relevance with atherosclerosis, especially Homer2correlation with apoptosis. Overexpression of Homer2,with vascular smooth muscle cells apoptosis increased, but interfering is not significantly with cell proliferation and apoptosis. These results indicate that, Homer2has some relevance with the formation of atherosclerosis...