Abstract 16414: Changes in the Adhesion of the Cardiomyocytes of Patients With Ischemic Cardiomyopathy are Highly Related to Depressed Left Ventricular Function
Introduction: Cell adhesion is essential for the proper organization and function of tissues, allowing the process of cardiac contraction in the myocardium. Several molecules are involved in cell binding, such as cadherins and connexins in intercellular junctions and integrins in cell-matrix junctions. Although numerous studies have found abnormalities in some of these molecules in the cardiac tissue of patients with heart failure (HF), the molecular details involved in these changes are not known yet.
Methods: We performed an exhaustive analysis of the expression of genes related to cell adhesion using high-throughput RNA sequencing technology (RNA-Seq). Genetic analysis was performed in patients with dilated cardiomyopathy (DCM) (n=13) and ischemic cardiomyopathy (ICM) (n=13) compared with control hearts (CNT) (n=10). To study the behavior of differentially expressed genes we performed a functional analysis using the DAVID bioinformatics v6 0.7 data base. The morphology of the intercalated discs between HF patients and controls using transmission electron microscopy was compared.
Results: The functional analysis of genes related to cell adhesion revealed alterations in the expression (rate of change>1.3 and p<0.05). A total of 24 genes differentially expressed in HF vs CNT, of which 6 encode integrins and 18 encode molecules involved in intercellular junctions, were identified. Different types of cell junctions are represented by at least one protein encoded by the 18 genes with different expression between patients and controls (GJA3, p<0.0001; DSP, p<0.0001; CLDN9, p<0.0001; PVRL3, p<0.01; PCDHGA3, p<0.001; VCL, p<0.0001; ITGA1, p<0.01). We also observed an elevated inverse relationship between the expression of PCDHGA3 and left ventricular end-systolic diameter (r=-0.86, p<0.01) and fractional shortening (r=-0.86, p<0.01) in patients with ICM.
Conclusions: This study reveals altered cell adhesions in patients with HF. The use of RNA-Seq technology allows us to identify new genes involved in the cardiomyocyte binding with aberrant expression in HF. Changes in PCDHGA3 are related to depressed left ventricular function in ICM.
Author Disclosures: M. Rivera: None. M. Manzanares: None. A. Martinez: None. A. Ortega: None. C. Gil Cayuela: None. E. Tarazon: None. E. Rosello: None. M. Portoles: None.
- © 2014 by American Heart Association, Inc.