Elucidation of physiological significance of LOX-1 binding molecules

2015 Fiscal Year Final Research Report

• Project/Area Number: 25293063
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Shinshu University (2014-2015); National Cardiovascular Center Research Institute (2013)
• Principal Investigator: SAWAMURA Tatsuya 信州大学, 学術研究院医学系, 教授 (30243033)
• Research Collaborator: KAKINO Akemi 信州大学, 先鋭領域融合研究群バイオメディカル研究所, 助教 (00534637) ; FUJITA Yoshiko 信州大学, 学術研究院医学系, 助教 (30416218)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: LOX-1 / GPCR / クロストーク

Outline of Final Research Achievements

First, we investigated the significance of GPCR-LOX-1 complex formation. We found that LOX-1 could form a complex with a GPCR X as well as with the angiotensin II receptor AT1. Binding of oxidized LDL to LOX-1 induced GPCR X-mediated intracellular signal transduction as was the case with AT1. Concerning AT1-LOX-1 complex formation, we witnessed that administration of an AT1 antagonist to SHRSP suppressed high fat diet-induced arterial lipid deposition even at doses that do not affect blood pressure. Second, we found that association of LOX-1 and coagulation factors promotes thrombin generation depending on the doses of LOX-1 and a coagulation factor.
Association of LOX-1 with the above molecules to induce various biological effects would illustrate a wide variety of LOX-1 roles in pathology not limited to atherosclerosis.

Free Research Field

薬理学