2006 Fiscal Year Final Research Report Summary
Roll of Toll-like receptors in atherosclerotic lesion formation
| Project/Area Number |
17590733
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
KAWASHIMA Seinosuke Kobe University, Graduate School of Medicine, Medical researcher, 大学院・医学系研究科循環呼吸器病態学, 医学研究員 (10177678)
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| Project Period (FY) |
2005 – 2006
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| Keywords | atherosclerosis / Toll-like receptor / coronary artery disease / carotid artery / rabbits / peripheral monocytes |
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| Research Abstract |
Role of local expression of Toll-like receptors (TLRs) on the vessel wall in atherogenesis.
Atherosclerosis is now considered as a chronic inflammatory disease, and inflammation is closely related to immune systems. TLRs has been identified as key components of innate-immunity. We examined the role of local expression of TLRs at the vessel wall in the initiation of atherosclerosis. We transacted cDNA encoding human TLR2 and TLR4 into the carotid arterial vessel wall of rabbits fed high-cholesterol with the use of HVJ-liposome. The rabbits were transfected with (1) pCMV-β-gal, (2) empty vector, (3) TLR2, (4) TLR4, (5) TLR2+4. The transfected plasmids were mainly expressed in the media. Either TLR2 or TLR4 transfection induced only non-significant augmentation of atherosclerosis. Notably, transfection of TLR2- and TLR4- containing HVJ synergistically accelerated atherosclerosis and increased expressions of VCAM-1, ICAM-1, and MCP-1. Moreover, transfection of TLR2 and TLR4 resulted in syne
… More
rgistic activation of NF-κB at the vessel wall in vivo, and in vascular smooth muscle cells in vitro. Therefore, expressions of both TLR2 and TLR4 at the vessel wall synergistically accelerated atherosclerosis. The present study revealed the role of TLRs expressed locally at the vessel wall in the early stage of atherosclerosis.
Toll-like receptors (TLRs) expression on the monocytes as a risk coronary marker
We investigated whether the TLR4 expression levels on human peripheral monocytes were associated with serum hsCRP levels or the occurrence of coronary artery diseases (CAD). One hundred CAD patients and 100 non-CAD subjects were enrolled. Among the low-hsCRP subjects, the TLR4 expression levels were higher in CAD patients than in non-CAD subjects. Moreover, TLR4 expression levels in stable angina pectoris (SAP) patients were elevated compared with those in non-CAD subjects, and those in acute coronary syndrome patients were higher than SAP patient's even in low-hsCRP subjects. In conclusion, the combined measurement of serum hsCRP and the TLR4 expression on peripheral blood monocytes, especially among low-hsCRP subjects, may become a new coronary risk marker. Less
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