Barrett Tessa J, Schlamp Florencia, Muller Matthew, Lee Angela H, Cornwell Macintosh G, Luttrell Williams Elliot, Smilowitz Nathaniel R, Hochman Judith, Ruggles Kelly V, Reynolds Harmony R, Berger Jeffrey S
New York University Grossman School of Medicine, New York, New York, USA; Sarah Ross Soter Center for Women's Cardiovascular Research, NYU Grossman School of Medicine, New York, New York, USA.
New York University Grossman School of Medicine, New York, New York, USA; Sarah Ross Soter Center for Women's Cardiovascular Research, NYU Grossman School of Medicine, New York, New York, USA.
JACC Basic Transl Sci. 2025 Mar;10(3):307-322. doi: 10.1016/j.jacbts.2024.10.018. Epub 2024 Nov 15.
Although platelets play a critical pathogenic role in myocardial infarction (MI), few studies have characterized the MI platelet transcriptome in the acute or chronic setting in women. We report that transcripts associated with the actin cytoskeleton, Rho family GTPases, mitochondrial dysfunction, and inflammatory signaling are enriched in platelets from MI patients in the acute setting (n = 40, MI; n = 38, control) and do not significantly change over time. Furthermore, 79 platelet genes chronically elevated or suppressed after MI are associated with future cardiovascular events in an independent high-risk cohort (n = 135). Compared with women with MI with nonobstructive coronary arteries, platelets from women with MI and obstructive coronary artery disease were enriched in neutrophil activation and proinflammatory signaling pathways driven by increased tumor necrosis factor (TNF)-α signaling. Hierarchic clustering of the MI transcriptomic profile identified 3 subgroups with distinctive biological pathways and MI correlates. Our data demonstrate that platelets from MI patients are phenotypically different from MI-naïve patients in the acute and chronic settings and reveal a platelet transcriptomic signature with distinct clinical features.
尽管血小板在心肌梗死(MI)中起着关键的致病作用,但很少有研究对女性急性或慢性心肌梗死时的血小板转录组进行特征描述。我们报告,与肌动蛋白细胞骨架、Rho家族GTP酶、线粒体功能障碍和炎症信号相关的转录本在急性心肌梗死患者的血小板中富集(心肌梗死组n = 40;对照组n = 38),且不会随时间显著变化。此外,心肌梗死后长期升高或受抑制的79个血小板基因与一个独立的高危队列(n = 135)中的未来心血管事件相关。与非阻塞性冠状动脉心肌梗死的女性相比,阻塞性冠状动脉疾病心肌梗死女性的血小板中,中性粒细胞活化和由肿瘤坏死因子(TNF)-α信号增强驱动的促炎信号通路更为富集。心肌梗死转录组图谱的层次聚类确定了3个具有独特生物学途径和心肌梗死相关因素的亚组。我们的数据表明,急性和慢性心肌梗死患者的血小板在表型上与未患心肌梗死的患者不同,并揭示了具有不同临床特征的血小板转录组特征。