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

INTERNATIONAL JOURNAL OF CARDIOLOGY

卷:278

Article

Li, Wei ; Zhang, Fengxiao ; Ju, Chenhui ; Lv, Suying ; Huang, Kai

关键词: CD27;    CD70;    Acute myocardial infarction;    Inflammation;    Ventricular remodeling;   

DOI  :  10.1016/j.ijcard.2018.11.132

来源: Elsevier

【 摘 要 】

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 90AMI patientswere enrolled in the present study. The serumlevels of soluble CD27 (sCD27) in patientswere 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 CD31positive endothelial cells (P = 0.026) and a-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. (c) 2018 Elsevier B.V. All rights reserved.

【 授权许可】

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