Identification of an endogenous oxidized LDL blocker and elucidation of its regulatory mechanism of arteriosclerotic diseases

2015 Fiscal Year Final Research Report

• Project/Area Number: 25670133
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Shinshu University (2014-2015); National Cardiovascular Center Research Institute (2013)
• Principal Investigator: 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(特定雇用) (00534637)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 酸化LDL / 酸化LDL受容体 / 動脈硬化

Outline of Final Research Achievements

Oxidized LDL (oxLDL) is implicated in atherosclerosis. Despite their potential importance, however, endogenous inhibitors that block the interaction between oxLDL and its receptors have not been extensively studied. To address this issue, we investigated whether developmental endothelial locus-1 (Del-1) might function as an endogenous inhibitor of oxLDL. Del-1 selectively bound to oxLDL. Del-1 inhibited oxLDL uptake and oxLDL-induced cellular responses irrespective of the kind of scavenger receptor. Moreover, Del-1 overexpression attenuated atherogenesis in mice. These results suggested that disrupted balance among modified LDL, scavenger receptors, and protective molecules might lead to the progression of atherosclerosis.

Free Research Field

薬理学