Platelet microRNA-15b protects against high platelet reactivity in patients undergoing percutaneous coronary intervention through Bcl-2-mediated platelet apoptosis

被引：6

作者：

Wang, Jinghan ^{[1
]}

Yao, Yi ^{[1
]}

Zhang, Jiahui ^{[1
]}

Tang, Xiaofang ^{[1
]}

Meng, Xianmin ^{[1
]}

Wang, Miao ^{[1
]}

Song, Lei ^{[1
]}

Yuan, Jinqing ^{[1
]}

机构：

[1] Chinese Acad Med Sci & Peking Union Med Coll, Natl Ctr Cardiovasc Dis, Fuwai Hosp, State Key Lab Cardiovascular Dis, Beijing 100037, Peoples R China

来源：

ANNALS OF TRANSLATIONAL MEDICINE | 2020年 / 8卷 / 06期

基金：

中国国家自然科学基金;

关键词：

Platelet microRNA; platelet reactivity; platelet apoptosis; percutaneous coronary intervention (PCI); OF-FUNCTION POLYMORPHISM; ASSOCIATION TASK-FORCE; MYOCARDIAL-INFARCTION; ANTIPLATELET THERAPY; CLINICAL-OUTCOMES; CLOPIDOGREL; ACTIVATION; INHIBITION; TICAGRELOR; DEATH;

D O I：

10.21037/atm.2020.02.88

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: High platelet reactivity (HPR) and low platelet reactivity ( LPR) are associated with an increased risk of ischemic/bleeding events in patients undergoing percutaneous coronary intervention (PCI). The role platelet miRNAs carry out in platelet reactivity regulation is largely unknown. Methods: In this study, we profiled the expression pattern of platelet miRNA in patients undergoing PCI with HPR (n=4) and LPR (n=4) by miRNA microarray screening. The candidate miRNAs were further validated in a larger sample of 17 LPR and 22 HPR patients by quantitative reverse-transcription polymerase chain reaction (RT-qPCR), and miR-15b was found differentially expressed. MiR-15b mimic and inhibitor were transfected into MEG-01 cells, then Bcl-2 protein expression and cell apoptosis were assessed. The relationship between platelet reactivity and platelet apoptosis was further evaluated. ABT-737, a Bcl-2 inhibitor was used to induce platelet apoptosis in PCI patients in vitro, and the influence of enhanced platelet apoptosis on platelet reactivity was explored. Results: Two miRNAs were found to be differentially expressed in patients with LPR and HPR using microarray system. Furthermore, the expression of miR-15b, a miRNA known to induce cell apoptosis via targeting of Bcl-2, was confirmed by RT-qPCR (P=0.020) to be 1.4x higher in the platelets of LPR patients than in those of HPR patients. Overexpression of miR-15b was demonstrated to suppress Bcl-2 protein expression and enhance cell apoptosis in a megakaryocyte cell line (MEG-01). The platelets of LPR patients expressed lower levels of Bcl-2 protein than those of HPR patients, and an inverse relationship between platelet reactivity and platelet apoptosis was observed among 44 patients who underwent PCI. Inducing platelet apoptosis in PCI patients in vitro, we observed that their platelet reactivity was decreased in a dose-dependent manner. Conclusions: Through the promotion of platelet apoptosis, platelet miR-15b negatively regulates platelet reactivity in patients undergoing PCI. Platelet apoptosis may represent a novel antiplatelet target for overcoming HPR in PCI treatment.

引用

页数：17