2005 Fiscal Year Final Research Report Summary
STUDY ON THE SIGNIFICANCE OF LOX-1 IN OXIDATIVE STRESS-RELATED BIOLOGICAL RESPONSES
| Project/Area Number |
16390070
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
General pharmacology
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
SAWAMURA Tatsuya National Cardiovascular Center Research Institute, Department of Vascular Physiology, Director, 脈管生理部, 部長 (30243033)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGUCHI Saburo National Cardiovascular Center Research Institute, Department of Vascular Physiology, Chief, 脈管生理部, 室長 (00182436)
NAKANO Atsushi National Cardiovascular Center Research Institute, Department of Vascular Physiology, Research Staff, 脈管生理部, 室長 (90217787)
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| Project Period (FY) |
2004 – 2005
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| Keywords | oxidized LDL receptor / LOX-1 / oxidized LDL / endothelial cells / arteriosclerosis / intimal thickening |
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| Research Abstract |
We have identified the oxidized LDL receptor expressed in endothelial cells. After the discovery, roles of LOX-1 in oxidative stress-related pathological responses and diseases were suggested. In the present study, we have employed (1) rat model for balloon arterial injury and (2) LOX-1 overexpressing ApoEKO mice to explore the role of LOX-1 in intimal thickening after PTCA and in coronary atherosclerosis.
(1) Intima of rat carotid artery was injured by an inflated balloon catheter. The induction of the expression of LOX-1 was detected immediately after the injury by RT-PCR analyses. Immnohistochemistry with anti-LOX-1 antibody showed LOX-1 was localized in imedial smooth muscle cells n the early phase, in intimal smooth muscle cells in intermediate phase, and in regenerated endothelial cells in the late phase. Treatment with anti-LOX-1 antibody reduced the thickening of intima as well as infiltration of leukocytes and oxidative stress.
(2) Heart of the LOX-1 overexpressing ApoEKO mice was analyzed, being compared with ApoEKO mice. Deposition of oxidized LDL, oxidative stress, expression of adhesion molecules, infiltration of macrophages, and lipid deposition were increased in LOX-1 overexpressing mice compared with ApoEKO mice.
These results suggest that LOX-1 is involved in the pathology of intimal thickening after balloon arterial injury and lipid deposition under hyper lipidemia. In both models oxidative stress are increased and LOX-1,at least in part, enhances the oxidative stress in the lesion. Manipulating LOX-1 activity might be a novel therapeutic approach for in oxidative stress-related diseases including these diseases.
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