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Cellular and molecular life sciences : CMLS
May 21, 2022;79 (6): 309.

Role of LL-37 in thrombotic complications in patients with COVID-19.

Zilei Duan, Juan Zhang, Xue Chen, Ming Liu, Hongwen Zhao, Lin Jin, Zhiye Zhang, Ning Luan, Ping Meng, Jing Wang, Zhaoxia Tan, Yaxiong Li, Guohong Deng, Ren Lai
Author Information
  1. Zilei Duan: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China.
  2. Juan Zhang: Southwest Hospital, Third Military Medical University (Army Medical University, 29 Gaotanyan Street, Shapingba, Chongqing, 400038, China.
  3. Xue Chen: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China.
  4. Ming Liu: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China.
  5. Hongwen Zhao: Southwest Hospital, Third Military Medical University (Army Medical University, 29 Gaotanyan Street, Shapingba, Chongqing, 400038, China.
  6. Lin Jin: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China.
  7. Zhiye Zhang: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China.
  8. Ning Luan: Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Sino-African Joint Research Center, Center for Biosafety Mega-Science, Kunming Institute of Zoology, Kunming, 650223, Yunnan, China.
  9. Ping Meng: Department of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, 650041, Yunnan, China.
  10. Jing Wang: Department of Laboratory Diagnosis, Chongqing Public Health Medical Center, Public Health Hospital of Southwest University, 109 Baoyu Rd. Shapingba, Chongqing, 400038, China.
  11. Zhaoxia Tan: Southwest Hospital, Third Military Medical University (Army Medical University, 29 Gaotanyan Street, Shapingba, Chongqing, 400038, China.
  12. Yaxiong Li: Department of Cardiovascular Surgery, Yan'an Affiliated Hospital of Kunming Medical University, Kunming, 650041, Yunnan, China. yxyayy@163.com.
  13. Guohong Deng: Southwest Hospital, Third Military Medical University (Army Medical University, 29 Gaotanyan Street, Shapingba, Chongqing, 400038, China. gh_deng@hotmail.com.
  14. Ren Lai: Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou, 511458, China. rlai@mail.kiz.ac.cn. ORCID
PMID: 35596804 DOI: 10.1007/s00018-022-04309-y

Abstract

Blood clot formation induced by dysfunctional coagulation is a frequent complication of coronavirus disease 2019 (COVID-19) and a high-risk factor for severe illness and death. Neutrophil extracellular traps (NETs) are implicated in COVID-19-induced immunothrombosis. Furthermore, human cathelicidin, a NET component, can perturb the interaction between the SARS-CoV-2 spike protein and its ACE2 receptor, which mediates viral entry into cells. At present, however, the levels of cathelicidin antimicrobial peptides after SARS-CoV-2 infection and their role in COVID-19 thrombosis formation remain unclear. In the current study, we analyzed coagulation function and found a decrease in thrombin time but an increase in fibrinogen level, prothrombin time, and activated partial thromboplastin time in COVID-19 patients. In addition, the cathelicidin antimicrobial peptide LL-37 was upregulated by the spike protein and significantly elevated in the plasma of patients. Furthermore, LL-37 levels were negatively correlated with thrombin time but positively correlated with fibrinogen level. In addition to platelet activation, cathelicidin peptides enhanced the activity of coagulation factors, such as factor Xa (FXa) and thrombin, which may induce hypercoagulation in diseases with high cathelicidin peptide levels. Injection of cathelicidin peptides promoted the formation of thrombosis, whereas deletion of cathelicidin inhibited thrombosis in vivo. These results suggest that cathelicidin antimicrobial peptide LL-37 is elevated during SARS-CoV-2 infection, which may induce hypercoagulation in COVID-19 patients by activating coagulation factors.

Keywords

COVID-19 Coagulation factors Hypercoagulation LL-37 SARS-CoV-2

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Grants

  1. SAJC201606/Chinese Academy of Sciences
  2. XDB31000000/Chinese Academy of Sciences
  3. KFJ-BRP-008/Chinese Academy of Sciences
  4. XDA12040221/Chinese Academy of Sciences
  5. Youth Innovation Promotion Association (2017432)/Chinese Academy of Sciences
  6. 31930015/National Natural Science Foundation of China
  7. 81770464/National Natural Science Foundation of China
  8. 82104130/National Natural Science Foundation of China
  9. U2002219/National Natural Science Foundation of China
  10. 32002311/National Natural Science Foundation of China
  11. 2019FA006/Yunnan Provincial Science and Technology Department
  12. 2019FI014/Yunnan Provincial Science and Technology Department
  13. 2019FB127/Yunnan Provincial Science and Technology Department
  14. 202101AU070176/Yunnan Provincial Science and Technology Department
  15. 17QNP010/PLA Youth Talent Project
  16. COVID-19 Project 2020NCPZX01/Chongqing Science and Technology Commission
  17. 202001AT070128/Yunnan Provincial Postdoctoral Science Foundation

MeSH Term

Antimicrobial Cationic Peptides
Blood Coagulation Factors
COVID-19
Fibrinogen
Humans
SARS-CoV-2
Spike Glycoprotein, Coronavirus
Thrombosis
Cathelicidins

Chemicals

Antimicrobial Cationic Peptides
Blood Coagulation Factors
Spike Glycoprotein, Coronavirus
spike protein, SARS-CoV-2
Fibrinogen
Cathelicidins
Journal Article
Article has an altmetric score of 2

Word Cloud

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