title: Local expression of Toll-like receptor 4 at the site of ruptured plaques in patients with acute myocardial infarction.
abstract: Several reports suggest that a chronic inflammatory process plays a key role in coronary artery plaque instability and subsequent occlusive thrombosis. In a previous study, we found that TLR4 (Toll-like receptor 4) mediates the synthesis of cytokines in circulating monocytes of patients with AMI (acute myocardial infarction); however, it remains unclear whether TLRs are expressed at the site of the ruptured plaque in these patients. The aim of the present study was to determine whether TLR2 and TLR4 are expressed at the site of ruptured plaques in patients with AMI and to compare this with systemic levels. The study included 62 patients with AMI, 20 patients with SA (stable angina) and 32 subjects with a normal coronary angiogram (control). Local samples from the site of the ruptured plaque were taken from patients with AMI using aspiration catheterization. Systemic blood samples from the aorta were taken from patients with AMI and SA and controls. Systemic levels of TLR2 and TLR4 were higher in patients with AMI than in patients with SA and controls. In patients with AMI, local TLR4 levels were higher than systemic levels. There was no significant difference in TLR2 levels between local and systemic samples. TLR4 immunostaining was positive in infiltrating macrophages in ruptured plaque material. Cardiac events were observed in 16 patients with AMI at the time of the 6-month follow-up study. Local and systemic levels of TLR4 were higher in patients with AMI with cardiac events than in those without. These results indicate an increase in monocytic TLR4 expression not only in the systemic circulation, but also at the site of plaque rupture. In conclusion, expression of both systemic and local plaque TLR4 may be one of the mechanisms responsible for the pathogenesis of AMI.
authors.affiliation: Department of Internal Medicine II and Memorial Heart Center, Iwate Medical University School of Medicine, Uchimaru 19-1, Morioka 020-8505, Iwate, Japan.
authors.forename: Yuh
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Mamoru
authors.initials: M
authors.lastname: Satoh
authors.forename: Tomonori
authors.initials: T
authors.lastname: Itoh
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Minami
authors.forename: Yuji
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Akamura
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D002478:Cells, Cultured; D005260:Female; D005500:Follow-Up Studies; D018840:HSP70 Heat-Shock Proteins / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000628:therapy; D011859:Radiography; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D051195:Toll-Like Receptor 2 / Q000097:blood / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000097:blood / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4