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

跨膜 - JAM - A 和可溶性 JAM - A 之间的嗜性相互作用调节血栓炎症 ： 对冠状动脉疾病的影响。

• 影响指数: 9.531
• 发表时间: May 2022
• 来源期刊: JACC Basic Transl Sci
• DOI: 10.1016/j.jacbts.2022.03.003
• PMID: 35663628
• 文章类型: Journal Article
• 作者列表: Rath D,Rapp V,Schwartz J,Winter S,Emschermann F,Arnold D,Rheinlaender J,Büttcher M,Strebl M,Braun MB,Altgelt K,Uribe ÁP,Schories C,Canjuga D,Schaeffeler E,Borst O,Schäffer TE,Langer H,Stehle T,Schwab M,Geisler T,Gawaz M,Chatterjee M

关键词: ACM, all-cause mortality; ACS, acute coronary syndrome; ADP, adenosine diphosphate; CAD, coronary artery disease; CCS, chronic coronary syndrome; CE, combined endpoint; HC, homozygous carriers; IS, ischemic stroke; JAM-A; JAM-A, junctional adhesion molecule-A; MI, myocardial infarction; SNV; SNV, single-nucleotide variation; TRAP, thrombin receptor activating peptide; coronary artery disease; platelet; sJAM-A, soluble junctional adhesion molecule-A; smJAM-A, soluble murine junctional adhesion molecule-A; thrombo-inflammation

Abstract

Genetic predisposition through F11R-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 (F11R-SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both F11R-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.

摘要

通过F11R单核苷酸变异（SNV）的遗传易感性会影响冠状动脉疾病（CAD）患者的循环可溶性交界粘附分子-A（sJAM-A）水平。次要等位基因的纯合携带者（F11R-SNVsrs2774276，rs790056）显示血栓炎症sJAM-A的水平提高。F11R-SNV和sJAM-A均与CAD患者复发性心肌梗死的不良预后相关。CAD患者血小板表面相关JAM-A与血小板活化标志物相关活化的血小板脱落跨膜-JAM-A，产生促炎sJAM-A和携带JAM-A的微粒。血小板跨膜-JAM-A和sJAM-A作为同型相互作用伴侣夸大了血栓形成和血栓-炎性血小板单核细胞相互作用。干扰这种同型界面的治疗策略可能会调节心血管疾病中血栓性和血栓-炎性血小板反应，其中循环sJAM-A水平升高。