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Int J Cardiol. 2019 Mar 1;278:210-216. doi: 10.1016/j.ijcard.2018.11.132. Epub 2018 Dec 3.

The role of CD27-CD70 signaling in myocardial infarction and cardiac remodeling.

Author information

1
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
2
Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: huangkai1@hust.edu.cn.

Abstract

BACKGROUND:

CD4+ T cells are key players in regulating the inflammatory processes and physiological repair mechanisms engaged after acute myocardial infarction (AMI). Although signaling through the CD27-CD70 co-stimulatory pathway are known to be important in CD4+ T cell activation and proliferation in certain contexts, the role of the CD27-CD70 pathway in AMI remains unclear.

METHODS AND RESULTS:

A total of 43 control subjects, 42 unstable angina patients, and 90 AMI patients were enrolled in the present study. The serum levels of soluble CD27 (sCD27) in patients were measured, revealing a significant increase in serum sCD27 levels in AMI patients within 24 h of the cardiac event, after which they decreased. Correlation analyses revealed that serum sCD27 was positively correlated with cardiac troponin I (c-TnI) (r = 0.267, P = 0.011). When anti-CD70 antibody was used to block the CD27-CD70 pathway in MI model mice, we found that this treatment increased left ventricular end-diastolic dimension (LVEDD) (P < 0.01) and left ventricular end-systolic dimension (LVESD) (P < 0.01), and decreased ejection fraction (P < 0.01). Flow cytometric analysis revealed that the percentage of regulatory T cells was lower in blocking antibody-treated mice (P < 0.01), while neutrophils levels were higher (P < 0.01). The number of CD31-positive endothelial cells (P = 0.026) and α-smooth muscle actin-positive arterioles (P < 0.01) were significantly down-regulated in anti-CD70 treated-AMI mice. The formation of the extracellular matrix (ECM) was also impaired.

CONCLUSION:

Serum sCD27 may be a potential biomarker for AMI. Blockade of the CD27-CD70 pathway worsens cardiac dysfunction, aggravates left ventricular remodeling, and impairs scar healing after AMI, resulting in heart failure.

KEYWORDS:

Acute myocardial infarction; CD27; CD70; Inflammation; Ventricular remodeling

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