| The morbidity and mortality of cardiovascular disease is rapidly increase followed the change of life style and the acceleration of population aging tendency and the younger of cardiovascular disease, so the research about the development mechanism,prevention and therapy of cardiovascular disease is gradually accumulated in recent year. The proliferation and the apoptosis of vascular smooth muscle cells(VSMC) is the co-pathologic base in many cardiovascular disease, such as artherosclerosis,restenosis after interventional therapy and hypertension and so on, so the research of the proliferation and the apoptosis of vascular smooth muscle cells become the central issue on cardiovascular disease prevention and therapy.The VSMC is the only cell component in intermediate membrane of artery, including shrinkage phenotype and synthesis phenotype. The shrinkage type VSMC is differentiated cell and can not be proliferated. The synthesis type VSMC is dedifferentiation cell and can proliferated. Some research indicated that the VSMC can be changed from differentiation condition to dedifferentiation condition stimulated in vasoconstrictor substances and also can be migrated from intermediate membrane to endomembrane. The artherosclerosis and the restenosis of blood vessel and hypertension are because of the VSMC migration and proliferation, and which induce the thickening of endomembrane and the narrow of blood vessel .The artherosclerosis,the restenosis of blood vessel and the hypertension are happened for the migration and the proliferation of the VSMC in past opinion, but recent research showed that the apoptosis is participated in the process of the cardiovascular disease. In 1985, Thorball observed the cell apoptosis in small artery growth period in mice, the result revealed the apoptosis existence in normal VSMC. In recent year, the VSMC apoptosis was founded in the artherosclerosis,the restenosis of blood vessel and the hypertension. It is consider that the balance of VSMC proliferation and apoptosis will directly influence the quantity of VSMC which will determine the vessel wall thickness and the size of blood vessel.UⅡis a kind of polypeptide which is made of 11~15 amino acid, widely exists in many species from mollusks to mammals (including humans) .The structure of UⅡin different species are different, but all of them share a common C-terminal cyclic structure, namely, Cys -Phe -Trp– Lys– Tyr-Cys connected through disulfide, this structure from fish to mammals are highly conserved in evolution, it is the active center of UⅡ. UⅡprecursor mRNA was mainly expressed in the cardiovascular and nervous system, and it can also be detected in kidney, spleen, small intestine, thymus, prostate, pituitary and adrenal glands. UⅡreceptor (UT) is an isolated G protein-coupled receptor. In humans, UT expressed throughout the central nervous system, and in peripheral tissues, UT mainly expressed in the cardiovascular system, including ventricles, ventricular, aortic, smooth muscle cells of coronary and aorta, endothelial cells of coronary artery, coronary artery aneurysms and atherosclerotic plaque (especially lipid plaque within the smooth muscle cells and macrophages). UT also expressed in the pancreas and the spinal cord motor neurons, some brain tissue, skeletal muscle and bladder smooth muscle also has the distribution, while the venous endothelial and smooth muscle has no expression. UⅡI and UT had a high affinity, UⅡbinding with UT mediate a series of biological effects, and the effect of post-receptor through CAMP, PLC, phospholipase A2, Ca2+ involved in this process. The current study shows that cardiovascular activity of UⅡinclude:⑴Vasoconstrictor effect: UⅡhas a strong contraction of blood vessels and vasospasm, the artery has stronger role than vein, contraction intensity is greater than norepinephrine, angiotensin and endothelin.UⅡis the strongest vasoconstrictor substances so far.⑵Vasodilator effect: UⅡalso demonstrated some vasodilator effect, which was the only one bi-directional regulation vasoactive peptides.⑶Effects on cell: UⅡis an endogenous mitogen, the same dose of UⅡhad different effects on the different cells, for example, cardiac fibroblasts> airway smooth muscle cells> renal department mesangial cells> vascular smooth muscle cells.⑷On hemodynamic: UⅡcan cause animal or person systemic or local hemodynamic changes, which was related with dose. Small doses reduced peripheral resistance, increased cardiac output, increased coronary perfusion pressure, less affected on blood pressure; large doses increased peripheral resistance, reduced cardiac output, inhibited myocardial contraction, increased blood pressure, lowed coronary perfusion pressure and resulted in myocardial ischemia.Studies have shown that there was a significant difference in plasma levels of UⅡof atherosclerosis, myocardial infarction, interventional treatment, heart failure, cardiomyopathy and hypertension and other cardiovascular diseases compared with the normal population, and UⅡwas the strongest of vasoconstrictor substances so far, which was 8-110 times than ET-1, therefore the study of UⅡon VSMC proliferation and apoptosis has become really important.In this study, plasma levels of UⅡof hypertension, acute coronary syndrome patients was detected through RIA and compared with normal control group. On the basis of them, to detect the effect of UⅡon rat VSMC proliferation by MTT assay, to detect the effect of UⅡon rat VSMC apoptosis by TEM, TUNLE assay and FCM, and to detect the Bax/Bcl-2 cell ratio by immunohistochemical method.Clinical study of the experimental results showed that the plasma UⅡlevels in unstable angina and acute myocardial infarction patients were significantly lower than the healthy control group, and the plasma UⅡlevels between unstable angina pectoris and acute myocardial infarction patients have significant difference; the plasma UⅡlevels in patients with essential hypertension were significantly lower than the healthy control group, but plasma UⅡlevels between 2 grade and 3 grade of hypertension have no significant difference; the plasma UⅡlevels in the unstable angina patients with hypertension have no significant difference compared the patients with pure hypertension and those with pure unstable angina; the levels of UⅡhave no relevance with age, gender, BMI, triglyceride and cholesterol.Foundation study of the experimental results showed that UⅡaccelerate rat VSMC grow significantly , promote the proliferation of rat VSMC significantly, and its proliferation show a dose-dependent and time-dependent manner; UⅡat the higher concentration range promote apoptosis in rat VSMC in a dose-dependent manner; UⅡat 10-7mol/L concentration had no significant role on apoptosis of the rat VSMC in the early stage , caused apoptosis of the rat VSMC in the late stage; meanwhile, UⅡalso has a catalytic role on proliferation cycle of vascular smooth muscle cell, with the concentration of UⅡand the time increasing , cells ratio in G0/G1 phase gradually reduce, that of S phase and G2 / M phase gradually increased; With the increasing of UⅡconcentration, Bcl-2 protein expression have significant change, Bax protein expression gradually increased, and the Bcl-2/Bax ratio reduced; in 10-7mol / L of UⅡincubated culture medium of rat VSMC, Bcl-2, Bax protein expression was no significant difference in the early stage, but the Bax protein expression gradually increased in the late stage, which reduced Bcl-2/Bax ratio, UⅡmay be caused apoptosis rat VSMC by lowering the ratio of Bcl-2/Bax. These results show that UⅡin cardiovascular disease may be related to induce VSMC proliferation and apoptosis, but development of the specific role and pathogenesis of UⅡ-induced VSMC proliferation and apoptosis in the occurrence of cardiovascular disease must be further explored,The ratio of Bcl-2/ Bax decrease, UⅡpossibly induce the apoptosis of VSMC in this way. The results show that, UⅡas a newer vasoactive substances in recent years, which is related with the occurrence and development of coronary heart disease and hypertension, UⅡmay be involved in the formation of the AS plaque and the AS plaque stability; the mechanism and the strength of UⅡin the pathogenesis of coronary heart disease or hypertension;the change of UⅡlevels in cardiovascular disease may be related to the effect of UⅡon VSMC proliferation and apoptosis;UⅡmaybe induced VSMC apoptosis by lowering the ratio of Bcl-2/Bax.It is very complex that the role of UⅡ-induced VSMC proliferation and apoptosis in the occurrence and development of cardiovascular disease, it remains to be further explored. |
PDF Full Text Request