2013 Fiscal Year Final Research Report

Bone marrow-derived cell mobilization promotes the progression of atherosclerosis and tissue regeneration

Research Project

Project/Area Number	23790878
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Circulatory organs internal medicine
Research Institution	Juntendo University
Principal Investigator	SATO Yayoi 順天堂大学, 医学部, 非常勤助教 (20327810)
Project Period (FY)	2011 – 2012
Keywords	動脈硬化 / マクロファージ / T細胞 / 炎症細胞 / コラゲナーゼ / cyclophosphamide / ApoEノックアウトマウス
Research Abstract	Atherosclerosis is one of the chronic inflammatory diseases, and the primary cause of heart disease or stroke in western countries. We investigated the effects of cyclophosphamide (CPA), a well-known immunomodulator and anticancer drug, in a murine model of established atherosclerosis. Continuous oral administration of CPA inhibited disease initiation in apolipoprotein E deficient, fed a high fat diet. Continuous CPA administration prevented from macrophage influx into formed atherosclerotic plaques. Here, atheroma progression was not significantly different even though a trend towards less plaque formation was observed in CPA-treated as compared to carrier-treated mice. Chemotherapy regulates lymphoid population like TH1/ TH2 balance in vivo. Additionally, pulse CPA treatment improved plaque stability with the decrease of matrixmetalloproteinase-2 and -9 expression. Our data suggest chemotherapy has a possibility as an optional therapy for advanced atherosclerosis.

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