Abstract 19023: Distinct Remodeling of Mitral Valve Leaflets in Severe Myxomatous and Ischemic Mitral Regurgitation
OBJECTIVES: The mitral valve (MV) leaflets in severe MR undergo structural remodeling associated with multiple degenerative and adaptive changes. We hypothesized that the gene expression profiles of MV leaflets from patients with severe myxomatous MR (MMR) are distinct from those with severe ischemic MR (IMR), reflecting different underlying pathophysiologic processes.
METHODS: MVs were obtained from 11 MMR patients (9 m, 2 f; age= 60.5±11.9 y, LVEF=58.2±4.6%) and 6 IMR patients (3 m, 3 f, age= 66.5±6.7 y, LVEF=33.3±16.3%) undergoing surgery for severe MR. Hemodynamic abnormalities were similar in the two groups. Tissue RNA was extracted and cDNA were hybridized to the Affymetrix Gene Chip 1.1. Normalization and two-way ANOVA analysis were performed by Partek Genomics Suite. Only genes that resulted in >1.5 fold difference and p <0.05 were considered significantly altered.
RESULTS: Of ∼29,000 genes examined, 453 (1.6%) were differentially expressed between the two groups. Hierarchical clustering of the normalized fluorescence signal values for these genes successfully differentiated all the MMR from the IMR samples (Figure 1). Based on functional analysis, the most statistically enriched biological processes were development (MYH11, ACTA2, ECM1, MMP19), cell growth (IGF1, IGFBP3, ADAMTSL2), adhesion (MCAM, PCDH10, COL4A1) and metabolic processes (ACOT7, CYP4A11) as shown in Table 1.
CONCLUSIONS: MV leaflets in severe MMR and IMR exhibit distinct gene expression patterns, suggesting different pathophysiologic mechanisms are involved in the leaflet remodeling processes. Understanding such adaptive mechanisms can potentially provide therapeutic opportunities.
- © 2012 by American Heart Association, Inc.