title: Interleukin 18 and extracellular matrix metalloproteinase inducer cross-regulation: implications in acute myocardial infarction.
abstract: Circulating interleukin-18 (IL-18) is thought to promote atherosclerosis and cardiovascular complications such as plaque rupture. Atherosclerosis is also characterized by smooth muscle cell migration, a consequence of extracellular matrix (ECM) degradation regulated by metalloproteinases (MMPs). Because extracellular matrix metalloproteinase inducer (EMMPRIN) has been shown to promote plaque instability by inducing ECM degradation and MMP synthesis, we investigated whether a cross-regulatory interaction exists between IL-18 and EMMPRIN in human monocytes. EMMPRIN levels in monocytes were markedly greater in 20 patients with acute myocardial infarction (AMI) compared with 20 patients with stable angina pectoris or 20 healthy volunteers (control group). The levels of IL-18 and MMP-9 in serum were also significantly greater in the AMI group in comparison with the other 2 groups. IL-18 levels positively correlated with increased levels of EMMPRIN in monocytes. In vitro, the expression of EMMPRIN was increased in monocytes cultured with IL-18, and IL-18 secretion was augmented in monocytes cultured with EMMPRIN. Gene silencing of EMMPRIN by small interfering RNA reduced monocyte secretion of both IL-18 and MMP-9. In the present study, cross-regulation between IL-18 and EMMPRIN in monocytes was demonstrated. This interaction may amplify the inflammatory cascade and be responsible for increased monocytic MMP-9 serum levels in atherosclerosis, contributing to atherosclerotic plaque destabilization and subsequent AMI.
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Shuang-Lun
authors.initials: SL
authors.lastname: Xie
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Yu-Yang
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Hai-Feng
authors.initials: HF
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Bing-Qing
authors.initials: BQ
authors.lastname: Deng
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Shu
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Zi-Zhuo
authors.initials: ZZ
authors.lastname: Su
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Yong-Qing
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China.
authors.forename: Ru-Qiong
authors.initials: RQ
authors.lastname: Nie
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China; Guangdong Province Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou, China. Electronic address: drwjf@sina.com.
authors.forename: Jing-Feng
authors.initials: JF
authors.lastname: Wang
mesh_terms: D000787:Angina Pectoris / Q000097:blood; D051926:Basigin / Q000097:blood* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D020868:Gene Silencing; D006801:Humans; D020382:Interleukin-18 / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009000:Monocytes / Q000201:enzymology; D009203:Myocardial Infarction / Q000097:blood* / Q000201:enzymology / Q000473:pathology
chemical_list: C497886:BSG protein, human; D020382:Interleukin-18; D051926:Basigin; D020780:Matrix Metalloproteinase 9