title: Differential expression of Toll-like receptor 4 and human monocyte subsets in acute myocardial infarction.
abstract: OBJECTIVE
  To investigate the involvement of Toll-like receptor 4 (TLR4) expression on two monocyte subsets in the pathologic processes related to acute coronary syndrome. How monocytes, which have recently been shown to comprise two distinct subsets, mediate the process of coronary plaque rupture remains to be fully elucidated. Recent studies have shown that TLR4 is involved in monocyte activation of patients with accelerated forms of atherosclerosis.
  
  
  METHODS
  We enrolled 65 patients with acute myocardial infarction (AMI, n=22), unstable angina pectoris (UAP, n=16), and stable angina pectoris (SAP, n=27) who underwent coronary angiography and 15 healthy controls. The expression of TLR4 on two monocyte subsets (CD14(+)CD16(-) and CD14(+)CD16(+)) was measured by flow cytometry.
  
  
  RESULTS
  In patients with AMI, TLR4 was more expressed on circulating CD14(+)CD16(+) monocytes than on CD14(+)CD16(-) monocytes (p<0.001). The expression levels of TLR4 on CD14(+)CD16(+) monocytes were significantly elevated in patients with AMI compared with other 3 groups. TLR4 expression levels on CD14(+)CD16(+) monocytes were significantly elevated at the culprit site compared with the systemic level (p=0.044). The up-regulation of TLR4 on admission was remarkably decreased 12 days after AMI (p<0.001). In addition, plasma levels of tumor necrosis factor-α were positively correlated with TLR4 expression levels on monocytes in patients with AMI (r=0.47, p=0.027).
  
  
  CONCLUSIONS
  TLR overexpression on CD14(+)CD16(+) monocytes in AMI, as demonstrated both in the circulation and at the coronary culprit site, might be associated with the pathogenesis of AMI.
authors.affiliation: Department of Cardiovascular Medicine, Wakayama Medical University, Wakayama, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Kashiwagi
authors.forename: Toshio
authors.initials: T
authors.lastname: Imanishi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Ozaki
authors.forename: Keisuke
authors.initials: K
authors.lastname: Satogami
authors.forename: Tomizo
authors.initials: T
authors.lastname: Masuno
authors.forename: Teruaki
authors.initials: T
authors.lastname: Wada
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Nakatani
authors.forename: Kohei
authors.initials: K
authors.lastname: Ishibashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Komukai
authors.forename: Takashi
authors.initials: T
authors.lastname: Tanimoto
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Ino
authors.forename: Hironori
authors.initials: H
authors.lastname: Kitabata
authors.forename: Takashi
authors.initials: T
authors.lastname: Akasaka
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000276:immunology; D000789:Angina, Unstable / Q000276:immunology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D017023:Coronary Angiography; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000097:blood; D006801:Humans; D007564:Japan; D018950:Lipopolysaccharide Receptors / Q000097:blood; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000276:immunology*; D017452:Receptors, IgG / Q000097:blood; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D015854:Up-Regulation
chemical_list: D015415:Biomarkers; C428200:FCGR3B protein, human; D058851:GPI-Linked Proteins; D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein