PMID- 33166900 OWN - NLM STAT- MEDLINE DCOM- 20210617 LR - 20210730 IS - 1879-2472 (Electronic) IS - 0049-3848 (Linking) VI - 197 DP - 2021 Jan TI - Neutrophil extracellular traps exacerbate coagulation and endothelial damage in patients with essential hypertension and hyperhomocysteinemia. PG - 36-43 LID - S0049-3848(20)30584-3 [pii] LID - 10.1016/j.thromres.2020.10.028 [doi] AB - Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY in patients in EH, thereby predisposing them to a more hypercoagulable state. Using a modified-capture enzyme-linked immunosorbent assay (ELISA) method, we observed that cell-free DNA (CF-DNA) and myeloperoxidase DNA (MPO-DNA) in patients With EH and HHCY were significantly higher. The NET formation was also positively correlated with homocysteine levels, neutrophil-lymphocyte ratio (NLR), and hypercoagulable markers (thrombin-antithrombin complex, D-dimers). Furthermore, neutrophils from patients in EH with HHCY were found to be predisposed to amplified NET release when compared to patients in EH without HHCY or CTR. Coagulation function assays showed that NETs in patients With EH and HHCY resulted in a significantly increased ability to generate thrombin and fibrin than in those in EH without HHCY or CTR. These procoagulant effects of NETs in patients With EH and HHCY were markedly inhibited (approximately 70%) by the cleavage of NETs with DNase I. Isolated NETs from patients With EH and HHCY neutrophils also exerted a strong cytotoxic effect on endothelial cells (ECs), converted them to apoptosis. This study revealed a previously unrecognized association between the hypercoagulable state and neutrophils in patients With EH and HHCY. Therefore, blocking NETs may represent a new therapeutic objective for preventing thrombosis in these patients. CI - Copyright (c) 2020 Elsevier Ltd. All rights reserved. FAU - Li, Ji-He AU - Li JH AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Tong, Dong-Xia AU - Tong DX AD - Department of Oncology, Qingdao Municipal Hospital Group, Qingdao 266000, Shandong Province, China. FAU - Wang, Ying AU - Wang Y AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Gao, Lei AU - Gao L AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Liu, Yue AU - Liu Y AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Zhang, Xiao-Hui AU - Zhang XH AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Chen, Wen-Jia AU - Chen WJ AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Chi, Jin-Yv AU - Chi JY AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Liu, Na AU - Liu N AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Yang, Kelaier AU - Yang K AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Wang, Shi-Peng AU - Wang SP AD - Department of Cardiology, Second Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Xu, Yang AU - Xu Y AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Li, Yang AU - Li Y AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. FAU - Yin, Xin-Hua AU - Yin XH AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. Electronic address: yinxihua365@163.com. FAU - Liu, Wen-Xiu AU - Liu WX AD - Department of Cardiology, First Affiliated Hospital of Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. Electronic address: liuwx65240@163.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Retracted Publication DEP - 20201101 PL - United States TA - Thromb Res JT - Thrombosis research JID - 0326377 SB - IM RIN - J Thromb Haemost. 2021 Aug;19(8):2096. PMID: 33314547 MH - Blood Coagulation MH - Endothelial Cells MH - Essential Hypertension MH - *Extracellular Traps MH - Humans MH - *Hyperhomocysteinemia/complications MH - Neutrophils OTO - NOTNLM OT - Endothelial cells OT - Essential hypertension OT - Hyperhomocysteinemia OT - Neutrophil extracellular traps OT - Platelets EDAT- 2020/11/10 06:00 MHDA- 2021/06/22 06:00 CRDT- 2020/11/09 20:19 PHST- 2020/06/08 00:00 [received] PHST- 2020/10/25 00:00 [revised] PHST- 2020/10/26 00:00 [accepted] PHST- 2020/11/10 06:00 [pubmed] PHST- 2021/06/22 06:00 [medline] PHST- 2020/11/09 20:19 [entrez] AID - S0049-3848(20)30584-3 [pii] AID - 10.1016/j.thromres.2020.10.028 [doi] PST - ppublish SO - Thromb Res. 2021 Jan;197:36-43. doi: 10.1016/j.thromres.2020.10.028. Epub 2020 Nov 1.