Homophilic Interaction Between Transmembrane-JAM-A and Soluble JAM-A Regulates Thrombo-Inflammation: Implications for Coronary Artery Disease

Genetic predisposition through single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles ( SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory...

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Published in:JACC. Basic to translational science 2022-05, Vol.7 (5), p.445-461
Main Authors: Rath, Dominik, Rapp, Vera, Schwartz, Jessica, Winter, Stefan, Emschermann, Frederic, Arnold, Daniel, Rheinlaender, Johannes, Büttcher, Manuela, Strebl, Michael, Braun, Michael B, Altgelt, Konstanze, Uribe, Álvaro Petersen, Schories, Christoph, Canjuga, Denis, Schaeffeler, Elke, Borst, Oliver, Schäffer, Tilman E, Langer, Harald, Stehle, Thilo, Schwab, Matthias, Geisler, Tobias, Gawaz, Meinrad, Chatterjee, Madhumita
Format: Article
Language:English
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Leading Edge Translational Research
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Summary:Genetic predisposition through single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles ( SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both SNVs and sJAM-A are associated with worse prognosis for recurrent myocardial infarction in CAD patients. Platelet surface-associated JAM-A correlate with platelet activation markers in CAD patients. Activated platelets shed transmembrane-JAM-A, generating proinflammatory sJAM-A and JAM-A-bearing microparticles. Platelet transmembrane-JAM-A and sJAM-A as homophilic interaction partners exaggerate thrombotic and thrombo-inflammatory platelet monocyte interactions. Therapeutic strategies interfering with this homophilic interface may regulate thrombotic and thrombo-inflammatory platelet response in cardiovascular pathologies where circulatory sJAM-A levels are elevated.
ISSN:2452-302X
DOI:10.1016/j.jacbts.2022.03.003