Toll-like receptor expression level on circulating monocyte in atherosclerotic disease

• Project/Area Number: 20590831
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Kagoshima University
• Principal Investigator: ORIHARA Koji Kagoshima University, 医歯学総合研究科, 特任助教 (90457664)
• Co-Investigator(Kenkyū-buntansha): HAMASAKI Syuichi 鹿児島大学, 医歯学総合研究科, 准教授 (10315434) ; ISHIDA Sanemasa 鹿児島大学, 医学部・歯学部附属病院, 講師 (30444889) ; TEI Cyuwa 鹿児島大学, 医歯学総合研究科, 教授 (10163891)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000); Fiscal Year 2010: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2009: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2008: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
• Keywords: 臨床 / 内科 / 循環器・高血圧 / 感染症 / トール様レセプター2 / 動脈硬化形成 / 動脈硬化性疾患 / 危険因子 / 末梢血単球 / 動脈硬化発生

Research Abstract

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). 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. The results demonstrated that 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. In conclusion, high TLR2 expression level on monocytes may be an independent risk factor for atherogenesis

Research Products

• [Journal Article] Reevaluation of quantitative flow cytometric analysis for TLR2 on monocytes using F(ab')2 fragments of monoclonal antibodies. (2011)
  • Author(s): Oba R, Orihara K, Kumagai T, Hirai H, Nagata K, Hamasaki S, Tei C, Masataka N.
  • Journal Title: Cytometry A. 79(4) Pages: 247-55
  • Peer Reviewed
• [Journal Article] Reevaluation of quantitative flow cytometric analysis for TLR2 on monocytes using F(ab')2 fragments of monoclonal antibodies. (2011)
  • Author(s): Orihara K, Hamasaki S, Tei C.
  • Journal Title: Cytometry A. Volume: 79 Pages: 247-55
  • Peer Reviewed
• [Journal Article] High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease. (2010)
  • Author(s): Kuwahata S, Fujita S, Orihara K, Hamasaki S, Oba R, Hirai H, Nagata K, Ishida S, Kataoka T, Oketani N, Ichiki H, Iriki Y, Saihara K, Okui H, Ninomiya Y, Tei C.
  • Journal Title: Atherosclerosis. 209(1)(Epub 2009 Aug 31) Pages: 248-254
  • Peer Reviewed
• [Journal Article] High expression level of Toll-like receptor 2 on monocytes is an important risk factor for arteriosclerotic disease. (2010)
  • Author(s): Orihara K, Hamasaki S, Ishida S, Tei C.
  • Journal Title: Atherosclerosis Volume: 209 Pages: 248-54
  • Peer Reviewed
• [Journal Article] The role of infection in the development of non-valvular atrial fibrillation : up-regulation of Toll-like receptor 2 expression levels on monocytes. (2009)
  • Author(s): Ichiki H, Orihara K, Hamasaki S, Ishida S, Oketani N, Iriki Y, Ninomiya Y, Okui H, Kuwahata S, Fujita S, Matsushita T, Yoshifuku S, Oba R, Hirai H, Nagata K, Tei C.
  • Journal Title: J Cardiol. 53(1) Pages: 127-135
  • NAID: 10025182813
  • Peer Reviewed
• [Journal Article] The role of infection in the development of non-valvular atrial Fibrillation : Up-regulation of Toll-like receptor 2 expression levels on monocytes (2009)
  • Author(s): 市来仁志
  • Journal Title: J Cardiol. 53 Pages: 127-135
  • Peer Reviewed
• [Journal Article] High expression level of Toll-like receptor 2 on monocytes is an important risk factor for atherosclerotic disease (2009)
  • Author(s): 桑波田聡
  • Journal Title: Atherosclerosis (in press)
  • Peer Reviewed
• [Presentation] Role of Infectious Inflammation for Atherogenesis : Toll-like Receptor 2 vs. C-reactive Protein. (2009)
  • Author(s): So Kuwahata, Shoji Fujita, Koji Orihara, Shuichi Hamasaki, Tetsuro Kataoka, Keishi Saihara, Sanemasa Ishida, Hitoshi Ichiki, Naoya Oketani, Yuichi Ninomiya, Hideki Okui, Ryutaro Oba, Hiroyuki Hirai, Kinya Nagata, Chuwa Tei
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Biomarker to predict the AF recurrence after catheter ablation for non-valvular atrial fibrillation. (2009)
  • Author(s): Ichiki H, Orihara K, Ishida S, Oketani N, Iriki Y, Ninomiya Y, Okui H, Matsushia T, Fujita S, Kuwahata S, Oba R, Hirai H, Nagata K, Hamasaki S, Tei C.
  • Organizer: 日本循環器学会
  • Place of Presentation: 大阪
  • Year and Date: 2009-03-20
• [Presentation] Role of Infectious Inflammation for Atherogenesis : Toll-like Receptor 2 vs. C-reactive Protein (2009)
  • Author(s): 桑波田聡
  • Organizer: 第73回日本循環器学会総会・学術集会
  • Place of Presentation: 大阪国際会議場, リーガロイヤルホテル(大阪市)