A Novel Pathway of Platelet Activation in ACS Mediated by LL-37 Immunoglobulin G Autoantibody Immune Complexes

IF 8.4 1区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS JACC: Basic to Translational Science Pub Date : 2024-07-01 DOI:10.1016/j.jacbts.2024.04.012
Paul C. Dimayuga PhD , Kuang-Yuh Chyu MD, PhD , Xiaoning Zhao PhD , Jianchang Zhou PhD , Nicole Wai Man Lio BS , Fernando Chernomordik MD , Daniel Berman MD , Prediman K. Shah MD , Bojan Cercek MD, PhD
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Abstract

The cathelicidin antimicrobial peptide LL-37 is a self-antigen in neutrophil extracellular traps that provokes autoantibody responses in autoimmune/autoinflammatory conditions. LL-37 immunoglobulin (Ig) G autoantibody levels were measured in subjects with and without atherosclerotic cardiovascular disease assessed using the coronary artery calcium score, in patients who had a future myocardial infarction and in a cohort of acute coronary syndrome (ACS) patients. LL-37 IgG levels were not associated with coronary artery calcium score, but future myocardial infarction patients had significantly higher LL-37 IgG at baseline. Reduced LL-37 IgG in ACS was associated with increased LL-37 IgG–immune complex. ACS plasma increased activated CD62P+ platelets from healthy donors mediated in part by LL-37 IgG–immune complexes and platelet Fc gamma receptor 2a.

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由 LL-37 免疫球蛋白 G 自身抗体免疫复合物介导的 ACS 中血小板活化的新途径
柔毛苷抗菌肽 LL-37 是中性粒细胞胞外捕获器中的一种自身抗原,在自身免疫/自身炎症情况下会引起自身抗体反应。在使用冠状动脉钙化评分评估患有和未患有动脉粥样硬化性心血管疾病的受试者、未来发生过心肌梗死的患者以及急性冠状动脉综合征(ACS)患者队列中测量了 LL-37 免疫球蛋白 (Ig) G 自身抗体水平。LL-37 IgG 水平与冠状动脉钙化评分无关,但未来心肌梗塞患者的基线 LL-37 IgG 水平明显更高。ACS 患者 LL-37 IgG 的降低与 LL-37 IgG 免疫复合物的增加有关。ACS 血浆增加了健康捐献者的 CD62P+ 活化血小板,部分原因是 LL-37 IgG 免疫复合物和血小板 Fc γ 受体 2a 的介导。
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来源期刊
JACC: Basic to Translational Science
JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-
CiteScore
14.20
自引率
1.00%
发文量
161
审稿时长
16 weeks
期刊介绍: JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.
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