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The Serum Levels Of Matrix Metalloproteinase2, 9(MMP-2, 9)in Patients Of Heart Failure

Posted on:2008-02-16Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y LiuFull Text:PDF
GTID:2144360212497100Subject:Clinical Medicine
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Backgrounds:chronic heart failure is one of the cardiovascular diseases that have undergone greatest increase in incidence and morbidity. Recently a quarter of patients who have suffered other cardiovascular diseases would be involved into CHF ultimately, which threatens the quality and safety of our human life to a great extent, especially the old people. With the development of the medicine science, people have had some new recognitions about the mechanism of heart failure, such as the necrosis and apoptosis of the cardiac muscle cells,the activation of neuroendocrine hormone and so on . The most important component element of the progress of CHF is the pumping disfunction , which always correlates with the alternation of myocardial structure of the left ventricular. We also call the alternation left ventricular(LV) remolding, which calls for many complicated mechanisms.LV remolding,which includes the hypertrophy of the myocardial cells and the increase in extracellular matrix(ECM), often leads to the alternation of myocardial structure,function and phaenotype.It has been researched recently that the main cause of CHF is the imbalance of myocardial ECM. The composition and organization of ECM in the myocardium are largely composed of a complex network of fibrillar collagen. The synthesis and degradation of myocardial ECM will keep a balance at normal state; however, once at pathologic state the ECM will lose its balance and cause LV dilatation as well as myocardial remolding, which will lead to CHF ultimately. ECM remolding is now recognized as a central process underlying the maladaptive reorganization of cardiac size,shape,and function during the progression of CHF.Matrix metalloproteinases(MMPs) mainly involve the remolding of ECM. MMPs are members of a family of Zn-dependent endopeptidases which derived from normal cells,inflammatory rumors that are responsible for degradation of ECM. MMPs often exist at the form of proenzyme and they could almost degrade all components of ECM. So far, nearly 25 different human MMPs have been found and are divided into 5 types including gelatinase, collagenase, and so on. MMPs could not only degrade the basement membrace and interstitial substance, but also play an important part in maining the balance between the ECM.An imbalance in the expression or activity of MMPs correlates with many diseases such as cardiovascular disease, pulmonary disease, arthritis or cancers and so on. So MMPs have been the hot spot studied by scientists abroad or in domestic country. It has been demonstrated that MMPs correlate with numbers of cardiovascular disease including coronary artery disease, dilated cardimyopathy and acute myocardial infarction. Animal models of cardiovascular disease further support a role for MMPs in cardiac remodeling. The subfamily of gelatinases includes MMP-2 and MMP-9. The gelatinases mainly degrade colleague typeⅣ﹑Ⅴ﹑Ⅶ. Recently research have reported that MMP-2 and MMP-9 correlate compactly with CHF. MMP-2 and MMP-9 expression and activation elevated in order to promote the degradation of myocardial ECM., which could cause LV dilation, ventricular wall thining and ventricular disfunction, which will ultimately lead to CHF. CHF can be divided into two types including systolic heart failure(SHF) and diastolic heart failure(DHF).The diagnosis, treatment and prognosis of the two types of heart failure diverse due to the different etiopathogenisis between SHF and DHF. In our experiment we investigate the expression and activation of MMP-2 and MMP-9 between SHF and DHF for the reason that they correlate compactly with CHF. Our research will do much good to the study of the diagnosis and treatment of CHF and provide wider ,faster and deeper extention for the inhibitor of MMPs which is for the use of treating CHF.Objectives: To investigate the serum levels of expression of MMP-2 and MMP-9 in SHF, CHF and control groups respectively for the purpose of approaching the internal relationship between MMP-2, MMP-9 and CHF. Through the way, we could further study whether MMPs can be regarded as a new target to evaluate the progressing as well as the treatment and prognosis of CHF.Methods: The expression of MMP-2 and MMP-9 were examined by SDS-PAGE zymograph in 40 SHF patients, 40 DHF patients and 20 healthy people as control group.Results:Compared with control group, both MMP-2 and MMP-9 were much higher in SHF and DHF groups(all p<0.05).There is no evident difference about the level of MMP-2 in SHF and DHF groups(p>0.05).However, in SHF guoup,the level of MMP-2 in sever SHF group(SHF1group) is much higher than mild SHF group(SHF2group) (p<0.05).Compared with DHF group,the level of MMP-9 was much higher in SHF group (p<0.05).Conclusions: The expression of MMP-2﹑MMP-9 were much higher in SHF and DHF groups compared with control group. It demonstrated that MMP-2 and MMP-9 be a diagnostic index of CHF. The level of MMP-9 is higher in SHF guoup than DHF group so we could conclude that MMP-9 may be more correlate with LV dilation. In SHF group, the level of MMP-2 in SHF2 group is higher than in SHF1 group,consequently the expression of MMP-2 could be a index of evaluating the progressing of SHF. Through the way, we could further study whether MMPs can be regarded as a new target to evaluate the progressing as well as the treatment and prognosis of CHF.
Keywords/Search Tags:Matrix Metalloproteinases, Systolic heart failure, Diastolic heart failure
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