Study On The Relationship Between MMP-9, MCP-1 And Atherosclerosis In Patients With Hypertension And Insulin Resistance

Background:Atherosclerosis (AS) is an evolutional inflammatory vascular disease and the heart, brain vascular diseases which due to it are serious health hazard to human life, also one of the diseases which mainly causes death and disabled in developed countries. In recent years, atherosclerosis inflammation theory get more and more attention of the researchers. The indeed mechanism of AS formation is not clear, but liprid infiltration, thrombogenesis and injury response are the three major theory. Ross introduced that"atherosclerosis is an inflammation disease not simple due to lipidoses."based on injury response, this got generally identification and reconstruction. In 1988, Reaven introduced that insulin resistance (IR) was the biological effect which produced by insulin was lower than prediction the first time. Many investigations had disclosed the close relationship among IR, inflammation and AS, there maybe some relationship between IR and AS through inflammation mechanism, at the same time some investigation indicated that IR not accelerated AS directly but through accelerating dyslipidemia and other metabolism accelerated AS indirectly, and often accompanying with hypertension, obesity, diabetes, hyperlipemia, coronary heart disease, stroke ect. Although some investigators have the contrary standpoint, most evidence supported IR accelerating the progress of AS. The relationship maong hypertension , IR and AS also got generally accredit, but the mechanism is also not clear. In recent years the relationship between matrix metalloproteinase-9 ( MMP-9) , monocyte chemoattractant protein-1 (MCP-1 ) and AS is also getting attention gradually. MMP-9 is a kind of matrix metalloproteinase. The arterial lesions promote the occurrence of AS development through the structural sclerosis which was caused by endothelial cells, extracellular matrix and lipid accumulation. While MMP-9 has a closely relationship with the degradation of extracellular matrix, especially takes an important position in atherosclerotic plaque of fibrous cap formation and destruction, considered having a closely relationship with the stability of the atherosclerotic plaque. But some recent studies suggest that MMP-9 also played a pivotal role in the early and progress stage of AS, and there are also some links with AS risk factors such as high blood pressure, high blood sugar, blood lipid disorders, etc. MCP-1 is a monocyte chemotactic factor which mainly though attracting monocyte and T lymphocytes, inducing monocyte and endothelial cell to express adhesion molecules and variety of inflammatory cells, especially attracting mononcytes to the lesion aggregation and responsing to inflammatory factors to infuluence the process of atherosclerosis directly. Some studys found that MCP-1 levels and the risk factors of atherosclerosis such as high blood pressure, hyperglycemia, blood fat disorders are also closely related, this suggested that MCP-1 may also express the impact of the process of atherosclerosis through some indirect way. Current studies of MMP-9, MCP-1 mainly focus on animal models or atherosclerotic plaque testing. There is little study of serum MMP-9, MCP-1 levels of the hypertension patients.Objective: Investigate the relationship of serum MMP-9, MCP-1 between atherosclerosis in patients with hypertension with insulin resistance, and to explore the possible mechanisms of the formation of AS and the risk factors. Provide a theoretical basis for the application of using them in clinical treatment and prognosis.Method: According bring and remove standard option, Sixty essential hypertension patients who had visited the out-patient clinic or had accept hospitalization in first hospital of jilin university were recruited.According to the level of homeostasis model assessment(HOMA-IR),HOMA-IR≥2.8 as the standard of IR, twenty-seven patients were classified as essential hypertension without insulin resistant (EH without IR), and thirty-three as essential hypertension with insulin resistant (EH with IR). Another 20 healthy individuals were selected as the control group. Blood pressure, height, weight were measured, fasting serum glucose, insulin, triglycerides, total cholesterol, high density lipoprotein-cholesterol and low density lipoprotein-cholesterol were also analyzed; HOMA-IR was calculated as a measture of insulin resistance;serum concentrations of MMP-9 and MCP-1 levels were measured by the Elisa method; common carotid artery intima-mediathickness (CCA- IMT ) and inner diameter were measured by logic9 colour ultrasonography.Result: (1) CCA-IMT in patients of control group, EH without IR and EH with IR were increase gradually,and compare each of them there is a statistical significance (P<0.05); (2) Serum concentrations of MMP-9,MCP-1 in patients of control group ,EH without IR and EH with IR were increase gradually,and compare each of them there is a statistical significance (P<0.05); (3) In patients with hypertension, both IR and CCA-IMT were positively correlated with serum concentration of MMP-9(r=0.460,P=0.003;r=0.514,P=0.001);both IR and CCA-IMT were positively correlated with serum concentration of MCP-1(r=0.564,P=0.002;r=0.588,P=0.002);there was positive correlation between MMP-9 and MCP-1(r=0.620,P=0.001);there was positive correlation between CCA-IMT and IR(r=0.675,P=0.002).Conclusions : (1) Hypertension is a atherosclerosis risk fantor;(2) IR is also a risk factor of athrosclerosis;(3) when IR accompany with hypertension maybe accelerate the proceeding of athrosclerosis coorperated; (4) Serum concentrations of MMP-9 and MCP-1 have the positive relationship with insulin resistant and, when withing insulin resistant maybe accelerate the proceeding of athrosclerosis coorperated.