New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction
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BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSIONS: 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.
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A previous study showed a link between ventricular expression of another gamma protocadherin, PCDHGA3, and cardiac dysfunction in individuals with ischemic cardiomyopathy.
“although a previous study showed a link between the ventricular expression of another gamma protocadherin, PCDHGA3, and cardiac dysfunction in individuals with ischemic cardiomyopathy.58”
From Aortic valve-specific genes dysregulated in calcific aortic valve stenosis as potential biomarkers and therapeutic targets (2025) · cites this paper as [58]
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- Authors
- Ortega, A., Gil-Cayuela, C., Tarazón, E., García-Manzanares, M., Montero, J. A., Cinca, J., Portolés, M., Rivera, M., & Roselló-Lletí, E.
- Affiliations
- Instituto de Investigación Sanitaria La Fe (ES)
- Hospital Universitari i Politècnic La Fe (ES)
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- PLOS ONE
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- Public Library of Science (PLoS)
- Published
- 2016-07-29
- Volume
- 11
- Issue
- 7
- Pages
- e0160168
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4966940
- OpenAlex
- W2505710817
- Cited by
- 30
- References
- 47
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 1 · 2021: 3 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3
- FWCI
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- journal article
- Language
- en
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- doi.org
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- PubMed Central (publishedVersion, cc-by)
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- Figshare (submittedVersion, cc-by)
- Funders
- Instituto de Salud Carlos III (PI13/00100, PI14/, PI14/01506)
- European Regional Development Fund
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- ischemic cardiomyopathy, protocadherins, adhesion molecules, intercalated discs, adherens junctions, desmosomes, gap junctions, ventricular dysfunction, stroke volume, ejection fraction, left ventricular dimensions, myocardial transcriptome, gene expression
- MeSH terms
- Cadherin Related Proteins, Female, Humans, Male, Middle Aged, Stroke Volume, Blotting, Western, Cell Adhesion Molecules, Gene Expression, Myocardial Ischemia, Sequence Analysis, RNA, Ventricular Dysfunction, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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