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The Levels Of Metalloproteinases/Tissue Inhibitor Of Matrix Metalloproteinases And Proinflammatory Cytokines After Treatment Of Heart Failure Due To Cardiomyopathy

Posted on:2011-04-21Degree:DoctorType:Dissertation
Country:ChinaCandidate:C N MaFull Text:PDF
GTID:1114360305983337Subject:Internal Medicine
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Objectives:Change of the expression of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase-1 (TIMP-1) and interleukin-18 (IL-18) in serum have been demonstrated in heart failure due to cardiomyopathy (DCM and ICM). However, the short effect of treatment on the levels of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 in patients with DCM or ICM has not been elucidated. In this study we measured levels of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 in serum of heart failure patients due to DCM and ICM, and age-matched normal subjects as control group. And we compared the above parameters before treatment with those after one week treatment.MethodWe enrolled 51 subjects in our hospital from March 2008 to April 2009. It contained 13 age-matched healthy subjects as control group and 38 patients as treatment group which involved 29 DCM and 9 ICM. Age range is 42-85 years. The diagnosis criteria was based on the patient's history, physical examination results, electrocardiography, echocardiography and cardiac catheterization. Left Ventricular ejection fraction (LVEF) of all patients were less than 45%, and left ventricular end diastolic diameter (LVEDD) were more than 52mm by echocardiography examination. Patients received standard medical treatment of heart failure, and combinated application of medications, including ACE inhibitors, angiotensin receptor blockers, nitrates, diuretics, digitalis, spironolactone and beta-adrenergic Blockers for almost one week until the heart failure symptoms improved. Blood samples were drawn from the peripheral vein during the admission time and one week after heart failure symptoms attenuated and the levels of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 in serum were measured by Enzyme Linked Immunosorbent Assay (ELISA)ResultsThe serum levels of MMP-1(15.43±12.64 VS 340.88±229.23), MMP-3 (13.78±16.94 VS 292.83±229.11), IL-18 (41.06±50.62 VS 977.42±510.48), IL-15 (87.72±142.64 VS 998.42±457.89) in DCM patients and IL-18 (67.66±118.77 VS 977.42±510.48), IL-15(129.28±197.11 VS 998.42±457.89) in ICM patients were significantly lower compared to control group before treatment (P<0.05), but there was no significant difference between DCM and ICM groups. The serum level of TIMP-1 in DCM patients were significant higher after treatment compared to that before treatment (5.04±16.88 VS 4.36±16.25, P<0.05), but not the serum levels of MMP-1, MMP-3, IL-18 IL-15 in DCM group and IL-18 IL-15 in ICM group.ConclusionAfter a period of one week treatment, the serum levels of TIMP-1 were significantly higher in DCM patients. Therefore the improvement of heart failure after one week of standard treatment could affect the expression of TIMP-1 in DCM patients. Objectives:Change of matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinase-1 (TIMP-1) and interleukin-18 (IL-18) have been demonstrated in the heart failure at the present. However the differences of expression of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18, IL-15 in NYHA functional class II and NYHA functional class III-IV due to DCM disease after short effect of treatment have not been elucidated. In this study we measured serum level of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 in heart failure (NYHA functional class II and NYHA functional class III-IV) treatment group and control group. And then compare the above parameters in NYHA functional class II with NYHA functional class III-IV before and after one week standard treatment.MethodsWe enrolled 42 subjects in our hospital from March 2008 to April 2009. It contained 13 age-matched healthy subjects as control group and 29 patients as treatment group which involved 7 NYHA functional class II and 22 NYHA functional class III-IV.Age range is 42-85 years. The diagnosis criteria were based on the patient's history, physical examination results, electrocardiography, echocardiography, and cardiac catheterization. Left Ventricular ejection fraction (LVEF) of all patients were less than 45%, and left ventricular end diastolic diameter (LVEDD) were more than 52mm by echocardiography examination. Patients were received standard medical treatment of heart failure, and combinated application of medications, including ACE inhibitors, angiotensin receptor blockers, nitrates, diuretics, digitalis, spironolactone and beta-adrenergic Blockers for almost one week until the heart failure symptoms improved. Blood samples were drawn from the peripheral vein during the admission time and one week after heart failure symptoms attenuated and the levels of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 in serum were measured by Enzyme Linked ImmunoSorbent Assay (ELISA)ResultsThe serum level of MMP-1 (16.94±16.93 VS 340.88±229.23), MMP-3 (24.62±30.07 VS 292.83±229.11), IL-15 (187.14±254.89 V S 998.42±457.89) IL-18 (63.92±78.53 VS 977.42±510.48) in NYHA functional class II patients and the serum levels of MMP-1 (15.01±11.68 VS 340.88±229.23), MMP-3 (10.53±9.57 VS 292.83±229.11), IL-15 (56.08±64.97 V S 998.42±457.89), IL-18 (34.52±39.85 VS 977.42±510.48) in NYHA functional class III-IV patients were significantly lower than control group before treatment (P<0.05), but there were no significant difference between NYHA functional classⅡand NYHA functional class III-IV after treatment. And the serum level of MMP-9, TIMP-1 in NYHA functional class II, NYHA functional class III-IV had no significant difference compared to control group before treatment and compared to NYHA functional class II and NYHA functional class III-IV after treatment.ConclusionAfter a period of one week treatment, there were no difference in the expression of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18, and IL-15 between NYHA functional class II and NYHA functional class III-IV. Therefore a short period of treatment of heart failure do not affect the expression of MMP-1, MMP-3, MMP-9, TIMP-1, IL-18 and IL-15 between NYHA functional classⅡand NYHA functional class III-IV.
Keywords/Search Tags:Cardiomyopathy, Heart failure, metalloproteinases, Tissue inhibitor of metalloproteinases-1, Interleukins
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