ABSTRACT
OBJECTIVE: To observe the expression of extracellular matrix metalloproteinase inducer (EMMPRIN) in the unstable plaque of patients with acute coronary syndrome (ACS), and the impact of leukotriene B4 (LTB4) on the EMMPRIN expression in macrophages. METHODS: The EMMPRIN expression was detected by immunohistochemistry in 11 unstable plaques from patients with ACS. Protein expression of EMMPRIN was evaluated by Western blot on macrophages differentiated from THP-1 which were stimulated with LTB4 in the absence or presence of LTB4 antagonist U75302. There are 8 study groups: 1-THP-1, 2-8-the macrophages derived from THP-1, 2-6-macrophages were stimulated by LTB4 (0, 10(-10), 10(-9), 10(-8) and 10(-7) mol/L) for 24 h, 7-8-the macrophages were pretreated by 10(-6) mol/L or 10(-7) mol/L U75302 2 h before the LTB4 (10(-7) mol/L) stimulation. RESULTS: Abundant EMMPRIN expression was detected in macrophages and smooth muscle cells of unstable plaques from ACS patients. As to the THP-1 derived macrophages, EMMPRIN expression was significantly upregulated in a concentration-dependent manner in LTB4 stimulated groups, which was significantly higher in group 3-6 than in the THP-1 group (group 1) and macrophages group (group 2) (all P < 0.05) and pretreatment with U75302 significantly reduced the LTB4 induced upregulation of EMMPRIN in a dose-dependent manner (P < 0.05). CONCLUSION: EMMPRIN expression is enhanced in macrophages and smooth muscle cells on unstable coronary artery plaques from ACS patients. LTB4 could stimulate EMMPRIN expression on THP-1 derived macrophages suggesting that LTB4 and EMMPRIN might be both involved in the formation and progression of unstable plaques, future studies are warranted to explore if LTB4 and EMMPRIN antagonists are effective or not for treating patients with ACS.
Subject(s)
Acute Coronary Syndrome/metabolism , Basigin/metabolism , Leukotriene B4/metabolism , Macrophages/metabolism , Plaque, Atherosclerotic/metabolism , Acute Coronary Syndrome/pathology , Cell Line , Humans , Leukotriene B4/pharmacology , Macrophages/drug effects , Myocytes, Smooth Muscle/drug effects , Myocytes, Smooth Muscle/metabolismABSTRACT
OBJECTIVES: To investigate the association between matrix metalloproteinase (MMP)-1(-1607 1G/2G), MMP-3(-1171 5A/6A), and MMP-9(-1562 C/T) polymorphism and susceptibility to idiopathic dilated cardiomyopathy (IDCM). DESIGN AND METHODS: MMP-1, -3, -9 genotypes were determined by PCR-RFLP analysis. RESULTS: Genotype frequency of MMP-3, but not MMP-1 and MMP-9 in IDCM patients, was significantly different from that in healthy controls. CONCLUSIONS: Our data suggested that MMP-3 5A/6A polymorphism could be a risk factor for the susceptibility to IDCM.
