The Change Of CPT-1 And GLUT-4 In Vascular Smooth Muscle Cells Of Rabbit During Atherosclerosis

The pathogenesy of atherosclerosis is complicated extremely. There are several theories to explain it from different point of view. Vascular smooth muscle cells play a very important role in atherogenesis, proliferation, migration and producing extracellular matrix are the essential characteristics of it. The biological behaviour is accompanied energy consumption. During atherogenesis, vascular smooth muscle cells proliferate, migrate from tunica intima to media and uptake lipid then become foam cells. We conclude that energy metabolism are changed of vascular smooth muscle cells during atherogenesis.We observe the change of two key enzyme for lipid metabolism and glucose metabolism within vascular smooth muscle cells to explain the question.Objective To investigate the change of carnitine palmitoyltransferase-1(CPT-1)and Glucose transporter-4(GLUT-4) in vascular smooth muscle tissue during atherosclerosis at 8th,16th,24th week after high-cholesterol diet to rabbit to determine whether atherogenesis is associated with the changes of vascular smooth muscle tissue energy metabolism, to provide a thinking for pathogenesy of atherosclerosis.Methods 36 rabbits were randomly and equally assigned to control group and high-cholesterol diet group, fed ordinary animal feeds to control group and fed high-cholesterol animal feeds to model group. Serum total cholesterol (TC), triglyceride and low density lipoprotein cholesterol (LDLC) were examined at the end of 8th, 16th and 24th week. At the same time, we studied histological changes of aorta by HE staining and histomorphometry analysis; and detected the gene expression of CPT-1 and GLUT-4 in vascular smooth muscle tissue of aorta thoraces by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively; last, we observe the protein expression of CPT-1 and GLUT-4 by immunohistochemical method, respectively.Results a. Compared with control group, the serum lipid and lipoprotein concentrations of model group were increased(P<0.05). b. Pathomorphology indicated that the ratio of aortic intimae to media (I/M), the thickness of aortic intimae add media (I+M), the ratio of the area of intimae to media (SI/SM) was increased when high-cholesterol diet lasting(P<0.05). c.16 and 24 weeks after high-cholesterol diet, the atherosclerosis formed and expression of CPT-1 mRNA and protein were reduced, compared with that of 16th week; CPT-1 was reduced at the end of 24th week. The expression of GLUT-4 mRNA was raised at the end of 16th and 24th week, but the expression of the protein was raised at 16th week, and then reduced at 24th week.Conclusion During atherosclerosis of rabbit, the expression of CPT-1 mRNA and its protein was downregulated in vascular smooth muscle cells, the GLUT-4 mRNA was upregulated but its protein was upregulated first and then downregulated. It indicates the decreasing of fatty acid utilization while increasing of glucose utilization in vascular smooth muscle cells during the earlier period of atherosclerosis, but the decreasing of fatty acid and glucose utilization in advanced stage of atherosclerosis. We conclude that there exists energy dysmetabolism in vascular smooth muscle cells during atherosclerosis.