Elevated plasma interleukin-37 playing an important role in acute coronary syndrome through suppression of ROCK activation

Abstract

// Tengyu Yang 1, * , Fang Fang 2, * , Yawen Chen 1 , Jing Ma 1 , Zhaowen Xiao 1 , Songfeng Zou 1 , Na Zheng 1 , Dewen Yan 4 , Songyan Liao 1 , Shaoyuan Chen 3 , Hongchen Fang 3 , Chekmen Yu 2 , Jie Liu 1 , Ming Dong 1 1 Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China 2 Division of cardiology, Department of Medicine and Therapeutics, Prince of Wales Hospital, Li Ka Shing Institute of Health and Sciences, Institute of Vascular Medicine, The Chinese University of Hong Kong, Hong Kong, China 3 Cardiology Division, Department of Medicine, The Nanshan Hostipal, Shenzhen, Guangdong, China 4 Department of Endocrinology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China * These authors have contributed equally to this work Correspondence to: Ming Dong, email: dongm@szu.edu.cn Keywords: interleukin -37, acute coronary syndrome, ROCK activity Received: October 15, 2016     Accepted: November 24, 2016     Published: December 25, 2016 ABSTRACT Objective : The plasma level of interleukin-37 is elevated in patients with acute coronary syndrome, however, its function during the onset and progress of the disease remains unclear. This study aimed to investigate the clinical significance of IL-37 in acute coronary syndrome and its underlying mechanism. Methods : 124 patients with acute coronary syndrome and 40 healthy controls were recruited in this study. Plasma interleukin-37 levels were measured in 41 patients with ST elevation myocardial infarction (STEMI), 41 patients with non-STEMI, 42 patients with unstable angina, and 40 controls. Mortality was defined as an event. Results : In this study, the mean follow-up period was 824±306 days (2-1077 days). 22% (n=27) of patients died. The mortality rate was significantly lower in patients with interleukin-37 serum levels below the median (6.4 pg/mL) than those with interleukin-37 serum levels above 6.4 pg/mL at 36-month follow-up (16% vs. 24%, p=0.02, log rank X 2 =5.39). Highly concentration of the anti-inflammatory interleukin-37 exerted a protective effect by suppressing the activated Rho Kinase (ROCK) activity in the peripheral blood mononuclear cells in vivo and in vitro after ischemia/reperfusion injury and stimulation of the Rho activator, calpeptin. Conclusions : The interleukin-37 level is significantly increased in acute coronary syndrome. Elevated baseline interleukin-37 levels in patients on admission are associated with poor outcomes. Thus, we propose that interleukin-37 could be a biomarker predictive of mortality in acute coronary syndrome. Moreover, this study reveals that the protective effect of interleukin-37 against atherosclerosis may involve the inhibition of ROCK activity.