Abstract 18918: Distinct Gene Expression Profiles of the Mitral Valve Leaflets in Barlow’s Disease and Fibroelastic Defficiency
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 the posterior MV leaflets from patients with bileaflet prolapse (Barlow’s valves) are distinct from those with only posterior leaflet degeneration (fibroelastic deficiency or MMR), reflecting different underlying pathophysiologic processes.
Methods: MVs were obtained from 12 Barlow’s patients (9 m, 3 f; age= 59.8±12.2 y, LVEF=60.4±5.8%) and 17 MMR patients (10 m, 7 f, age= 54.2±6.6 y, LVEF=59.7±5.1%) undergoing surgery for severe MR. Normal MV were obtained from 6 unmatched donor hearts (4 m, 2 f, age= 41.5±10.7 y, LVEF=57.5±8.8%). RNA was extracted and cDNA microarray was carried on the Affymetrix Gene Chip 1.1. Normalization and two-way ANOVA analysis were performed. Only genes that resulted in >1.5 fold difference and p <0.05 were considered significantly altered.
RESULTS: Of ~29,000 genes examined, 973 (3.3%) were differentially expressed between the two disease groups. Principal component analysis and Hierarchical clustering of the normalized fluorescence signal values for these genes successfully differentiated all the Barlow’s from the MMR samples (Figure 1). Based on functional analysis, selected statistically significant enriched biological processes are listed in (table1).
Conclusions: MV leaflets in Barlow’s and MMR 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.
- © 2013 by American Heart Association, Inc.