The Comparisons Of TES Expression And The Impacts On Atherosclerosis Between Different Arteries In Rabbits

Background:Atherosclerosis(AS) is the leading cause of death and disability. AS is a multiple-cause disease, lipid deposition, plaque formation and inflammation in the arteries are its pathological changes, leading to vascular occlusion partially or completely, which cause multiple organ ischemia and infarction such as heart, brain or kidney. Large amount of research has shown that different arteries occur different degree of AS. Carotid artery and coronary artery(CA) are atherosclerotic-prone,while internal mammary artery(IMA) is atherosclerotic-resistant. Because of this difference, IMA was used in coronary artery bypass grafting(CABG) surgery. So far,the mechanism of the susceptibility of IMA has not been elucidated. We hypothesize that biological differences are the key to distinguish IMA from the CA in resistante of atherosclerotic development.Aim:To study the difference expression of the TES gene between IMA and CA and the reaction to high-fat feeding, we compared its expression between normal IMA and normal CA in control and 3-months’ high-fat feeding rabbits. Meanwhile, we measured the expression of TES gene in two sources of endothelial cell from original generation of cells of IMA and CA. By means of overexpression and knock-down TES gene in human umbilical vein endothelial cells, we observed the effects of TES gene on the function of endothelial cell to clarify the role of TES gene in the development of atherosclerosis.Methods:1. We observed the normal structure of IMA and CA and the expression and difference of TES m RNA and protein in IMA and CA respectively. Meanwhile, we used primary culture cells of rabbit IMA and CA to assess the expression of TES m RNA and protein in the different two sources of endothelia cells respectively.2. In the atherosclerotic model of 12-weeks’ high-fat feeding rabbit, the structural changes and occurrence of atherosclerosis of IMA and CA were observed. At the same time, we evaluated the expression of TES m RNA and protein before and after high-fat feeding.3. By constructing overexpression and knockdown TES gene in human umbilical vein endothelial cell, we analyze the influence of TES gene on growth, proliferation,adhesion, migration and apoptosis of endothelial cells, and investigate the molecularbiological mechanism of TES gene.Result:1. HE staining showed that the vascular wall structure can be divided into three layers as usual, that is tunica intima, tunica media and tunica adventitia, but the tunica media of IMA contains more elastic fiber, and smooth muscle cells are the main structure in CA. There is no difference in other structure between the two arteries. Expression of TES m RNA and protein was lowered in CA compared with IMA(P<0.05). The expression of TES from primary culture cells showed that the m RNA and protein quantity of TES are higer in IMA cells than CA cells(P<0.05).2. Compared with normal rabbits, blood lipid and weight of the 12-weeks’ high-fat feeding rabbits increased significantly, and the incidence of atherosclerosis in CA is higher than IMA(P<0.05); the expression of TES was reduced in CA compared with IMA after 12-weeks high-fat feeding(P<0.05). The expression of TES in IMA was increased after high-fat feeding, while its expression in CA is reduced after high-fat feeding(P<0.05).3. When TES is overexpressed in HUVECs, the cells showed higher ability of migration and but lower ability of adhesion and co-adhesion with THP-1 cells than control cells(P<0.05). Meanwhile, the ability of growth, apoptosis showed no statistical significant(P>0.05). When TES is knocked down in HUVECs, the cells showed higher ability of adhesion co-adhesion with THP-1 cells but lower ability of migration than control(P<0.05). At the same time, the ability of growth, apoptosis showed no statistical significant(P>0.05).Conclusion:These results demonstrated the association between TES gene and atherosclerotic-resistant IMA. It may inhibit monocytes from ahereing to endothelial cells and enhance the migration of endothelial cells at the same time. However, TES gene dose not affect the growth, proliferation and apoptosis of endothelial cells.