title: Elevated plasma interleukin-37 playing an important role in acute coronary syndrome through suppression of ROCK activation.
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 X2=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.
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Tengyu
authors.initials: T
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Ma
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Zhaowen
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Songfeng
authors.initials: S
authors.lastname: Zou
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Zheng
authors.affiliation: Department of Endocrinology, The First Affiliated Hospital of Shenzhen University, Shenzhen, China.
authors.forename: Dewen
authors.initials: D
authors.lastname: Yan
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Songyan
authors.initials: S
authors.lastname: Liao
authors.affiliation: Cardiology Division, Department of Medicine, The Nanshan Hostipal, Shenzhen, Guangdong, China.
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Cardiology Division, Department of Medicine, The Nanshan Hostipal, Shenzhen, Guangdong, China.
authors.forename: Hongchen
authors.initials: H
authors.lastname: Fang
authors.affiliation: 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.
authors.forename: Chekmen
authors.initials: C
authors.lastname: Yu
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Division of Pathophysiology, Medical College, Shenzhen University, Shenzhen, Guangdong, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Dong
mesh_terms: D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002478:Cells, Cultured; D016009:Chi-Square Distribution; D004151:Dipeptides / Q000494:pharmacology; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D000072658:Non-ST Elevated Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D011379:Prognosis; D012307:Risk Factors; D000072657:ST Elevation Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000201:enzymology / Q000401:mortality; D013997:Time Factors; D015854:Up-Regulation; D054460:rho-Associated Kinases / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D004151:Dipeptides; D020536:Enzyme Activators; C508587:IL37 protein, human; D007375:Interleukin-1; C071482:calpeptin; D054460:rho-Associated Kinases
keywords: ROCK activity; acute coronary syndrome; interleukin -37