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BMC Medicine
Published in: BMC Medicine 1/2019

Open Access 01-12-2019 | Myocardial Infarction | Research article

Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury

Authors: Yihua Bei, Li-Long Pan, Qiulian Zhou, Cuimei Zhao, Yuan Xie, Chengfei Wu, Xiangmin Meng, Huanyu Gu, Jiahong Xu, Lei Zhou, Joost P. G. Sluijter, Saumya Das, Birgitta Agerberth, Jia Sun, Junjie Xiao

Published in: BMC Medicine | Issue 1/2019

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Abstract

Background

Cathelicidins are a major group of natural antimicrobial peptides which play essential roles in regulating host defense and immunity. In addition to the antimicrobial and immunomodulatory activities, recent studies have reported the involvement of cathelicidins in cardiovascular diseases by regulating inflammatory response and microvascular dysfunction. However, the role of cathelicidins in myocardial apoptosis upon cardiac ischemia/reperfusion (I/R) injury remains largely unknown.

Methods

CRAMP (cathelicidin-related antimicrobial peptide) levels were measured in the heart and serum from I/R mice and in neonatal mouse cardiomyocytes treated with oxygen glucose deprivation/reperfusion (OGDR). Human serum cathelicidin antimicrobial peptide (LL-37) levels were measured in myocardial infarction (MI) patients. The role of CRAMP in myocardial apoptosis upon I/R injury was investigated in mice injected with the CRAMP peptide and in CRAMP knockout (KO) mice, as well as in OGDR-treated cardiomyocytes.

Results

We observed reduced CRAMP level in both heart and serum samples from I/R mice and in OGDR-treated cardiomyocytes, as well as reduced LL-37 level in MI patients. Knockdown of CRAMP enhanced cardiomyocyte apoptosis, and CRAMP KO mice displayed increased infarct size and myocardial apoptosis. In contrast, the CRAMP peptide reduced cardiomyocyte apoptosis and I/R injury. The CRAMP peptide inhibited cardiomyocyte apoptosis by activation of Akt and ERK1/2 and phosphorylation and nuclear export of FoxO3a. c-Jun was identified as a negative regulator of the CRAMP gene. Moreover, lower level of serum LL-37/neutrophil ratio was associated with readmission and/or death in MI patients during 1-year follow-up.

Conclusions

CRAMP protects against cardiomyocyte apoptosis and cardiac I/R injury via activation of Akt and ERK and phosphorylation and nuclear export of FoxO3a. Increasing LL-37 might be a novel therapy for cardiac ischemic injury.
Appendix
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Metadata
Title
Cathelicidin-related antimicrobial peptide protects against myocardial ischemia/reperfusion injury
Authors
Yihua Bei
Li-Long Pan
Qiulian Zhou
Cuimei Zhao
Yuan Xie
Chengfei Wu
Xiangmin Meng
Huanyu Gu
Jiahong Xu
Lei Zhou
Joost P. G. Sluijter
Saumya Das
Birgitta Agerberth
Jia Sun
Junjie Xiao
Publication date
01-12-2019
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2019
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-019-1268-y

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