Elucidation of roles of MMP-1 in atherosclerosis and plaque rupture using transgenic rabbits

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460486
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: University of Yamanashi
• Principal Investigator: NIIMI Manabu 山梨大学, 総合研究部, 助教 (80644898)
• Co-Investigator(Renkei-kenkyūsha): FAN Jianglin 山梨大学, 総合研究部, 教授 (60272192)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 動脈硬化 / 腹部大動脈瘤 / ウサギ / トランスジェニック / MMP-1

Outline of Final Research Achievements

Increased expression of matrix metalloprotease-1 (MMP-1) has been implicated in atherosclerosis and aneurysms; however, it is not fully understood whether macrophage-derived MMP-1 affects atherosclerosis and aneurysm. To investigate this hypothesis, we generated transgenic (Tg) rabbits expressing human MMP-1 in macrophages under the control of human scavenger receptor promoter. After feeding a cholesterol rich diet, MMP-1 Tg rabbits had similar lesion size of aortic atherosclerosis compared with non-Tg rabbits; however, Tg rabbits showed a remarkable destruction of the medial elastic lamina in the aortic lesions. Using an elastase-induced aneurysm model, we found that Tg rabbits showed grater aortic dilation than non-Tg rabbits. These results indicate that macrophage-derived MMP-1 plays an important role in pathogenesis of vascular disease.

Free Research Field

実験病理学