Abstract 12902: Association Between Matrix Metalloproteinases, Tissue Inhibitor of Metalloproteinase and Mitral Chordae Tendinae Rupture
Background: We previously found the association between hypertension and chordae tendinae rupture (CTR), a progressive disease eventually resulting in the need for mitral valve (MV) surgery. Understanding the pathogenesis of CTR is important in further identification of risk factors for early intervention. Matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinase (TIMP) trigger the signal cascade instigating cardiac remodeling and fibrosis possibly predisposing to CTR. We investigate the role of MMP and TIMP expression of MV complex in CTR.
Method: Using a cross-sectional study in a tertiary medical center in Taiwan, we enrolled 185 patients receiving MV replacement and classified them into two groups: 64 (35%) with CTR and 121 (65%) without CTR. Expression of MV MMP and TIMP, assessed on a semi-quantitative scale (0 to 3), was determined by immunohistochemical staining using antibodies against MMP1, MMP9, TIMP1 and TIMP2.
Result: Eighty-one (44%) of the patients were men with a mean age of 50.3±13.4 years old. The CTR patients have more male sex (p = 0.008), shorter disease duration from onset of symptom to surgery (DD, p < 0.001), higher prevalence of hypertension, coronary artery disease and pulmonary edema (all p <0.04), lower prevalence of rheumatic heart disease and atrial fibrillation (both p < 0.001), larger left ventricular end-diastolic dimension (LVEDD, p < 0.001), smaller left atrium dimension (p = 0.016), higher severity of mital regurgitation (MR, p < 0.001) and higher expression of MV MMP1, MMP9, TIMP1 and TIMP2 (all p < 0.001) than the patients without CTR. Using binary logistic regression analysis, the variation in CTR group was found to be independently explained by TIMP1 (p = 0.003, OR = 1.899, CI = 1.258-2.897), hypertension (p = 0.015, OR = 2.803, CI = 1.221-6.433), DD (p = 0.009, OR = 0.989, CI = 0.981-0.997), severity of MR (p<0.001, OR = 2.118, CI = 1.416-3.167) and LVEDD (p = 0.025, OR = 1.060, CI = 1.007-1.116).
Conclusion: Mitral expression of TIMP1 was associated with CTR in this study. Because it was observed independently of other MMP, TIMP and baseline characteristics, we think that the TIMP1 may play a role in the pathogenesis of CTR.
- © 2011 by American Heart Association, Inc.