New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction

Intercalated disks are unique structures in cardiac tissue, in which adherens junctions, desmosomes, and GAP junctions co-localize, thereby facilitating cardiac muscle contraction and function. Protocadherins are involved in these junctions; however, their role in heart physiology is poorly understo...

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Bibliographic Details
Published in:PloS one 2016-07, Vol.11 (7), p.e0160168-e0160168
Main Authors: Ortega, Ana, Gil-Cayuela, Carolina, Tarazón, Estefanía, García-Manzanares, María, Montero, José Anastasio, Cinca, Juan, Portolés, Manuel, Rivera, Miguel, Roselló-Lletí, Esther
Format: Article
Language:English
Subjects:
Adherens junctions
Adhesion
Analysis
Biology and Life Sciences
Blotting, Western
Cardiac muscle
Cardiology
Cardiomyopathy
Cell adhesion
Cell adhesion & migration
Cell adhesion molecules
Cell Adhesion Molecules - genetics
Cell Adhesion Molecules - metabolism
Desmosomes
Development and progression
Disks
Female
Gap junctions
Gene Expression
Gene sequencing
Genetic aspects
Health aspects
Heart
Heart diseases
Heart failure
Heart transplantation
Hemodynamics
Hospitals
Humans
Ischemia
Library collections
Male
Medical research
Medicine and Health Sciences
Mental depression
Middle Aged
Muscle contraction
Muscles
Myocardial diseases
Myocardial Ischemia - metabolism
Myocardium
Patients
Physiological aspects
Proteins
Protocadherin
Research and analysis methods
Ribonucleic acid
RNA
Sequence Analysis, RNA
Signal transduction
Statistics
Stroke
Stroke volume
Stroke Volume - genetics
Transcriptome
Transplantation
Ventricle
Ventricular Dysfunction - genetics
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Summary:Intercalated disks are unique structures in cardiac tissue, in which adherens junctions, desmosomes, and GAP junctions co-localize, thereby facilitating cardiac muscle contraction and function. Protocadherins are involved in these junctions; however, their role in heart physiology is poorly understood. We aimed to analyze the transcriptomic profile of adhesion molecules in patients with ischemic cardiomyopathy (ICM) and relate the changes uncovered with the hemodynamic alterations and functional depression observed in these patients. Twenty-three left ventricular tissue samples from patients diagnosed with ICM (n = 13) undergoing heart transplantation and control donors (CNT, n = 10) were analyzed using RNA sequencing. Forty-two cell adhesion genes involved in cellular junctions were differentially expressed in ICM myocardium. Notably, the levels of protocadherin PCDHGA3 were related with the stroke volume (r = -0.826, P = 0.003), ejection fraction (r = -0.793, P = 0.004) and left ventricular end systolic and diastolic diameters (r = 0.867, P = 0.001; r = 0.781, P = 0.005, respectively). Our results support the importance of intercalated disks molecular alterations, closely involved in the contractile function, highlighting its crucial significance and showing gene expression changes not previously described. Specifically, altered PCDHGA3 gene expression was strongly associated with reduced stroke volume and ventricular dysfunction in ICM, suggesting a relevant role in hemodynamic perturbations and cardiac performance for this unexplored protocadherin.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0160168