Effect Of Atorvastatin On Serum Matrix Metalloproteinase-9 Level In Patients With Acute Coronary Syndrome

PrefaceAtheromatous plaque rupture and subsequent thrombosis are the main causes of acute coronary syndrome ( ACS ). Matrix metalloproteinases ( MMPs) have the capability to degrade the extracellular matrix of the fibrous cap, predisposing to plaque rupture. Several lines of evidence suggest that MMP - 9 could play a potential role in atheromatous plaque disruption and in the molecular mechanism of ACS.Clinical trials have demonstrated that statin therapy reduces cardiovascular events and mortality. In addition to the effects on lipid concentrations, stabilization of atherosclerotic plaques and attenuation of the inflammatory response may account for the clinical benefits of statins in ACS. Animal experiments and clinical studies have shown that statins can stabilize plaque by increasing the collagen content and inhibiting metalloproteinases.The purpose of this study was to observe the influence of atorvastatin on serum matrix matalloproteiases -9(MMP -9) ,c -reactive protein (CRP) level in patients with acute coronary syndrome( ACS) and also compared with healthy individual control after taking atorvastatin for 2 weeks, so we can study the benefits of statins of stabilization of atherosclerotic plaques and attenuation of the inflammatory response.Materials and methodsFor this study, we enrolled 60 patients with ACS (including 30 patientswith AMI and 30 patients with UAP) , who were in their first episode. Twenty healthy individuals who were age - and sex - matched with patients served as controls. The patients of ACS received a combination of conventional therapy plus 40mg/day atorvastatin each evening for 2 weeks after onset of disease within with 48 hours. Conventional therapy included aspirin, beta -blocker, angioten-sin - converting enzyme inhibitor, low - molecular - weight heparin. Peripheral venous blood was drawn in heparin - containing tubes after overnight fasting at baseline and after 2 weeks to detect the concentrations of the MMP - 9, CRP, total cholesterol, triglycerides and LDL - cholesterol. MMP - 9 was determined u-sing enzyme -linked immunosorbent assay (ELJSA) kits according to the manufacturers instructions ( R&D Systems). The CRP samples were analysed by latex particle - enhanced immuno turbidimetric assay. All the data are expressed by x ± s, Comparisons between groups were analyzed by t - test (two - sided) , P value <0.05 (two-tailed) was considered statistically significant.Results1. The concentrations of MMP -9 and CRP at baseline : Patients with ACS had higher plasma MMP - 9 and CRP concentrations than those of the controls (P <0.05 for UAP group, P <0. 001 for AMI group). Patients with AMI had higher plasma MMP - 9 and CRP concentrations than those of the UAP (P < 0.01 for MMP - 9, P < 0.001 for CRP).2. The concentrations of MMP - 9 and CRP before and after 2 weeks therapy : After 2 weeks, plasma MMP - 9 and CRP had decreased significantly in both groups (P <0.05 for UAP group,P <0.001 for AMI group).3. The lipid level before and after 2 weeks therapy: After 2 weeks, total cholesterol, triglycerides, and LDL - cholesterol concentrations were significantly lower in all the patients with ACS( P < 0. 001). HDL cholesterol concentrations increased ( P < 0.05 ).DiscussionAtheromatous plaque rupture and subsequent thrombosis are the main causes of acute coronary syndrome ( ACS). Plaque instability is associated with a high macrophage content and a thin fibrous cap. Interstitial matrix components are responsible for resistance to rupture of an atherosclerotic plaque. The balance between matrix production and degradation is an important determinant of plaque stabilization. MMP enzymes may weaken the protective fibrous cap. Reduced MMP synthesis could be an important therapeutic goal. MMPs belong to the family of proteases. Macrophages are the major source of the MMPs, of which MMP - 9 is the most prevalent form. MMP - 9 degrades denatured collagen and elastin. Inflammatory activation of MMP - 9 may contribute to the enhanced matrix degradation. Expression of MMP - 9 in atherosclerotic plaque has the ability to induce collagen breakdown in vivo and in vitro.Inflammatory processes are involved in the initiation of acute coronary syndrome because they destabilize the atherosclerotic plaque and enhance the formation of thrombus. C - reactive protein is a sensitive acute - phase protein whose levels increase in response to inflammation, infection, and tissue damage. Some authors have suggested that C - reactive protein might not only mirror an underlying inflammatory process, but also directly interact with atherosclerotic vessels by activating the complement system, thereby promoting inflammation and thrombosis. The marker of C - reactive protein was a powerful predictor of acute cardiac events.Clinical trials have shown that statin therapy reduces rates of morbidity and mortality from coronary artery disease. The beneficial effects of statin therapy in primary prevention can be attributed to plaque stabilisation. Iipid accumulation in atherosclerotic plaque enhances inflammatory activity. Increased inflammatory activity strongly stimulates MMPs expression via cytokines. Statins reduce plaque Iipid core and increase extracellular matrix content. Statins have anti -inflammatory and anti - platelet effects, which are known as non - Iipid effects. Statin treatment can decrease endogenous inflammatory response that stimulatesMMPs enzyme production. Reduced plaque inflammation by statin treatment may result in suppressed MMPs activity. In the present study circulating MMP - 9 activity and CRP were studied before and after statin treatment. The results suggest that it is useful to have earlier lipid - lowing therapy with statins.Conclusions1. The present investigation shows that plasma concentrations of MMP - 9 and CRP in patients with ACS are significantly higher than those in controls, which suggests that MMP - 9 and CRP could serve as powerful predictors of unstable atherosclerotic plaques and as an indicator for early diagnosis of the patients with ACS.2. After 2 weeks therapy with atorvastatin, plasma MMP -9 and CRP had decreased significantly and total cholesterol, triglycerides, and LDL - cholesterol concentrations were significantly lower in both groups received a therapy of atorvastatin. In addition to the effects on lipid concentrations, stabilization of atherosclerotic plaques and attenuation of the inflammatory response may account for the clinical benefits of statins in ACS.