Correlation between Serum Markers of Adverse Left Ventricular Remodelling and Gene Expression Levels Measured in the Myocardial Tissue of Patients with Chronic Primary Mitral Regurgitation

Abstract

Telephone number: +32 (0)16 34 15 33, Fax number: +32 (0) 16 32 15 13, keir.mccutcheon@uzleuven.be ABSTRACT Background: Chronic primary mitral regurgitation (CPMR) is characterized by progressive myocardial hypertrophy, fibrosis and dilatation. Although molecular markers of adverse left ventricular (LV) remodelling have been identified in the progression from compensated to decompensated heart failure in these patients, serum markers that could guide the optimal timing of intervention in these patients are still needed. Here we describe the correlation between the levels of expression of several genes important in adverse LV remodelling in CPMR and the serum levels of these markers. Methods:We performed echocardiography, cardiac catheterization, endomyocardial biopsy (EMB) and serum analysis in patients with severe CPMR during the preoperative workup for mitral valve surgery. Serum levels of N-terminal-pro hormone B-type natriuretic peptide, suppression of tumourigenicity 2, tumour necrosis factor a, Interleukin 6, FS-7-associated surface antigen (FAS), FAS ligand, matrix metalloproteinase (MMP)-1, MMP-2, MMP-9, tissue inhibitor of matrix metalloproteinases (TIMP)-1 and TIMP-4 were determined using commercially available enzyme-linked immunosorbent assays. Myocardial levels of expression of the genes encoding these proteins were determined by multiplex gene expression analysis.Results: Serum and EMBs were obtained from 12 patients with CPMR at the time of preoperative cardiac catheterization. Overall, there was no significant correlation between the serum levels and gene expression levels for the markers evaluated in this study. A non-significant inverse correlation between serum MMP-2 and myocardial MMP-2 was noted (r = −0.343, P = 0.263). Conclusion:We found a poor correlation between the myocardial gene expression levels of several markers of adverse LV remodelling in patients with CPMR and the serum levels of these markers sampled at the same time.