High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease.
BACKGROUND
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns to initiate an innate immune response. We previously reported upregulation of TLR2 expression level on monocytes of stable angina pectoris patients with significant coronary artery disease (CAD) relative to control patients without significant CAD. In this study we aimed to determine whether high level of Toll-like receptor 2 (TLR2) is a risk factor for atherogenesis, independent of established risk factors including smoking, diabetes mellitus (DM), hypertension (HT), and hyperlipidemia (HL).


METHODS
TLR2 expression level on circulating monocyte surfaces was measured by using our developed flow cytometry assay. Patients were classified into two groups: "Arteriosclerotic disease" group (n=108) and "Control" group (n=70). Patients of the first group had arteriosclerotic disease such as CAD, aortic aneurysm, or peripheral arterial disease (PAD). The "Control" group was sex- and age-matched to the "Arteriosclerotic disease" group.


RESULTS
TLR2 expression was significantly higher in the "Arteriosclerotic disease" group than in the "Control" group (p<0.001). Multivariate ordinal logistic regression analysis was performed; other known risk factors, which were represented to two nominal score points, 0 or 1, for patients with and without it, respectively, and TLR2 level, which was treated as a metric variable. DM (p=0.002), HT (p=0.001), HL (p<0.001), and TLR2 level (p<0.001) were identified as significant contributors for arteriosclerotic disease.


CONCLUSIONS
High TLR2 expression level on monocytes may be an independent risk factor for atherogenesis.
Kuwahata
So
S
Department of Cardiovascular, Respiratory & Metabolic Medicine, Graduate School of Medicine, Kagoshima University, Sakuragaoka, Kagoshima, Japan.
Fujita
Shoji
S
Orihara
Koji
K
Hamasaki
Shuichi
S
Oba
Ryutaro
R
Hirai
Hiroyuki
H
Nagata
Kinya
K
Ishida
Sanemasa
S
Kataoka
Tetsuro
T
Oketani
Naoya
N
Ichiki
Hitoshi
H
Iriki
Yasuhisa
Y
Saihara
Keishi
K
Okui
Hideki
H
Ninomiya
Yuichi
Y
Tei
Chuwa
C
D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology* / Q000276:immunology*; D002097:C-Reactive Protein / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D012306:Risk; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis*
D051195:Toll-Like Receptor 2; D002097:C-Reactive Protein