Dataset Information

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

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.

SUBMITTER: Rath D

PROVIDER: S-EPMC9156439 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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

Rath Dominik D Rapp Vera V Schwartz Jessica J Winter Stefan S Emschermann Frederic F Arnold Daniel D Rheinlaender Johannes J Büttcher Manuela M Strebl Michael M Braun Michael B MB Altgelt Konstanze K Uribe Álvaro Petersen ÁP Schories Christoph C Canjuga Denis D Schaeffeler Elke E Borst Oliver O Schäffer Tilman E TE Langer Harald H Stehle Thilo T Schwab Matthias M Geisler Tobias T Gawaz Meinrad M Chatterjee Madhumita M

JACC. Basic to translational science 20220523 5

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 wit ...[more]

PMID: 35663628

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Project description:BackgroundCoronary artery aneurysm (CAA) and coronary artery ectasia (CAE) may be two different types of coronary artery dilatation with unknown etiology. This study aimed to compare the differences between CAA and CAE and to investigate their pathogenesis and the necessity of antiplatelet therapy.MethodsOne hundred patients each with confirmed CAA, CAE, and normal coronary artery (NCA) from September 2017 to July 2019 were included. All patients completed examinations of the ankle-brachial index (ABI), pulse wave rate, and carotid ultrasonography; and were tested for routine blood, lipid, and immune parameters. Blood samples were collected 1 week after the withdrawal of antiplatelet drugs, and vascular inflammatory indexes, platelet activation indexes, thromboelastography, and the platelet aggregation rate were measured. Analysis of variance and the chi-square or Fisher exact test were used for statistical analysis.ResultsThe perinuclear anti-neutrophil cytoplasmic antibody (ANCA), endothelial-1, matrix metalloproteinase-9, and tumor necrosis factor-α were significantly higher in CAE than in NCA, while cytoplasmic ANCA was appreciably higher in CAE than in CAA (P<0.05). Myeloperoxidase and growth/differentiation factor-15 were significantly higher in CAE than in CAA and NCA (P<0.05). ABI was significantly lower in CAA and CAE than in NCA (P<0.05), low-density lipoprotein/high-density lipoprotein was significantly higher in CAA than in NCA (P<0.05), and the detection rate of carotid artery thickening was significantly higher in CAA than in CAE and NCA (P<0.05). The Gensini and SYNTAX scores were significantly higher in CAA than in CAE (P<0.05). The percentages of CD62P and PAC-1 were higher in CAA and CAE than in NCA (P<0.05). The arachidonic acid aggregation rate in CAA and adenosine 5'-diphosphate aggregation rate in CAE were significantly higher than in NCA (P<0.05). The values of thrombin formation time and reaction time were significantly lower in CAE than in NCA (P<0.05), and the α angle was significantly higher in CAE than in NCA.ConclusionsCAE was closely related to inflammation, whereas CAA was closely related to atherosclerosis. Platelet activation was present in both diseases; therefore, antiplatelet therapy is recommended.

Project description:In the broad range of human diseases, thrombo-inflammation appears as a clinical manifestation. Clinically, it is well characterized in context of superficial thrombophlebitis that is recognized as thrombosis and inflammation of superficial veins. However, it is more hazardous when developed in the microvasculature of injured/inflamed/infected tissues and organs. Several diseases like sepsis and ischemia-reperfusion can cause formation of microvascular thrombosis subsequently leading to thrombo-inflammation. Thrombo-inflammation can also occur in cases of antiphospholipid syndrome, preeclampsia, sickle cell disease, bacterial and viral infection. One of the major contributors to thrombo-inflammation is the loss of normal anti-thrombotic and anti-inflammatory potential of the endothelial cells of vasculature. This manifest itself in the form of dysregulation of the coagulation pathway and complement system, pathologic platelet activation, and increased recruitment of leukocyte within the microvasculature. The role of platelets in hemostasis and formation of thrombi under pathologic and non-pathologic conditions is well established. Platelets are anucleate cells known for their essential role in primary hemostasis and the coagulation pathway. In recent years, studies provide strong evidence for the critical involvement of platelets in inflammatory processes like acute ischemic stroke, and viral infections like Coronavirus disease 2019 (COVID-19). This has encouraged the researchers to investigate the contribution of platelets in the pathology of various thrombo-inflammatory diseases. The inhibition of platelet surface receptors or their intracellular signaling which mediate initial platelet activation and adhesion might prove to be suitable targets in thrombo-inflammatory disorders. Thus, the present review summarizes the concept and mechanism of platelet signaling and briefly discuss their role in sterile and non-sterile thrombo-inflammation, with the emphasis on role of platelets in COVID-19 induced thrombo-inflammation. The aim of this review is to summarize the recent developments in deciphering the role of the platelets in thrombo-inflammation and discuss their potential as pharmaceutical targets.

Project description:BackgroundAs for the coronary artery inflammation and coronary atherosclerotic burden, which are used to assess the risk of adverse cardiac events in patients, it is unclear whether there is any certain correlation between them. Therefore, the purpose of this study was to explore the potential relationship between coronary artery inflammation and coronary atherosclerotic burden.MethodsA total of 346 eligible patients underwent assessment of computed tomography (CT) attenuation values of pericoronary adipose tissue (PCAT) in the right coronary artery and Agatston coronary artery calcium (CAC) based on coronary CT angiography. These measurements were utilized to evaluate coronary inflammation and atherosclerotic burden, respectively. Patients with a CAC score of 0 were categorized into groups based on the presence or absence of coronary artery disease (CAD). CAC scores of 10, 100, and 400 were chosen as cutoff values to compare differences in PCAT attenuation values across different CAC scores.ResultsWhen comparing all CAD patients to non-CAD patients, a significantly higher PCAT attenuation was observed in CAD patients (-87.54±9.39 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation in CAD patients with a CAC score of 0 was significantly higher than that in patients with a CAC score greater than 0 and in non-CAD patients with a CAC score of 0 (-82.63±8.70 vs. -90.38±8.59 vs. -93.45±7.42 HU, P=0.000). The PCAT attenuation values did not exhibit significant differences among different CAC scores (all P>0.05); however, it was highest in CAD patients with a CAC score of 0 (P<0.05). Body mass index, hyperlipidemia, hypertension, and PCAT attenuation were identified as independent risk factors in both CAD patients with a CAC score of 0 and patients with a CAC score greater than 0 (all P<0.05).ConclusionsThe results of this study suggest that a direct relationship between coronary inflammation and coronary atherosclerotic burden is not evident. Nonetheless, it is noteworthy that coronary inflammation was most pronounced in CAD patients with a CAC score of 0, while CAC score did not demonstrate an association with inflammation.

Dataset Information

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

Publications

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

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