Plasma active matrix metalloproteinases, MMP1 and MMP9, have potential implications on left atrial function and remodeling, in patients with coronary artery disease

Abstract Background Matrix metalloproteinases (MMPs), a family of proteolytic enzymes, are known to be involved in the regulation of turnover of extracellular matrix in cardiac tissue. Left atrial (LA) volume and function are an important predictor of mortality and morbidity after myocardial infarction. However, the impact of MMPs on structural atrial remodeling is not completely known. Aim To quantify the levels of MMP1 and MMP9, and to determine their association with left atrial volume, ejection fraction (EF), and global longitudinal strain (GLS) in patients with acute coronary syndromes (ACS) or chronic coronary syndromes (CCS). Methods 90 patients with coronary artery disease (61% men, 58+/-12 years), including 60 patients with ST-elevation acute myocardial infarction (STEMI), 30 patients with diabetes and 30 patients without diabetes, and 30 patients with CCS were assessed within 24 hours of admission by serum MMP-1 and MMP-9 analysis (ELISA kits). 2D echocardiography was used to assess LA volume and EF, and speckle tracking to asses GLS. Results (see figure). Circulating levels of MMP1 and MMP9 were significantly increased in patients with STEMI vs. CCS (95%CI 1.92-8.43, p=0.002). In general group evaluation, MMP1 correlated with minimum LA volume (r=0.29, p=0.007) and with LA expansion index (r=-0.31, p=0.004), active LAEF (r=-0.41, p=0.0001), total LAEF (r=-0.31, p=0.003), and also with maximum negative LA strain (r=-0.21, p=0.04), while MMP 9 correlated with expansion index of LA (r=-0.25, p=0.01), active LAEF (r=-0.21, p=0.05), and total LAEF respectively (r=-0.24, p=0.02). In patients with STEMI and diabetes, MMP1 correlated positively with maximum and minimum LA volume (r=0.44 and r=0.43, respectively, both p=0.02), while in patients with STEMI without diabetes, MMP9 correlated negatively with passive LAEF (r=-0.44, p=0.01) and expansion index (r=-0.51, p=0.004). Both MMP1 and MMP 9 did not have any significant correlation with atrial function parameters in patients with CCS. Conclusions Circulating microRNAs and MMPs are promising biomarkers involved in atrial remodeling, directly affecting collagen metabolism changes, and are correlated with some of the most important parameters of atrial function and deformation in STEMI patients. However, further studies are needed to establish the influence of their expression on the progress of atrial structural remodeling and progression to atrial fibrillation.