Smooth muscle cells healing atherosclerotic plaque disruptions are of local, not blood, origin in apolipoprotein E knockout mice

被引:108
作者
Bentzon, Jacob F.
Sondergaard, Claus S.
Kassem, Moustapha
Falk, Erling
机构
[1] Univ Aarhus, Inst Clin Med, Aarhus, Denmark
[2] Univ Aarhus, Dept Mol Biol, Aarhus, Denmark
[3] Odense Univ Hosp, Dept Endocrinol, DK-5000 Odense, Denmark
关键词
atherosclerosis; blood cells; muscle; smooth; thrombosis;
D O I
10.1161/CIRCULATIONAHA.107.722355
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background - Signs of preceding episodes of plaque rupture and smooth muscle cell ( SMC) - mediated healing are common in atherosclerotic plaques, but the source of the healing SMCs is unknown. Recent studies suggest that activated platelets adhering to sites of injury recruit neointimal SMCs from circulating bone marrow - derived progenitor cells. Here, we analyzed the contribution of this mechanism to plaque healing after spontaneous and mechanical plaque disruption in apolipoprotein E knockout (apoE(-/-)) mice. Methods and Results - To determine the origin of SMCs after spontaneous plaque disruption, irradiated 18-month-old apoE(-/-) mice were reconstituted with bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic apoE(-/-) mice and examined when they died up to 9 months later. Plaque hemorrhage, indicating previous plaque disruption, was widely present, but no bone marrow - derived eGFP(+) SMCs were detected. To examine the origin of healing SMCs in a model that recapitulates more features of human plaque rupture and healing, we developed a mechanical technique that produced consistent plaque disruption, superimposed thrombosis, and SMC-mediated plaque healing in apoE(-/-) mice. Mechanical plaque disruption was produced in irradiated apoE(-/-) mice reconstituted with eGFP(+) apoE(-/-) bone marrow cells and in carotid bifurcations cross-grafted between apoE(-/-) and eGFP(+) apoE(-/-) mice. Apart from few non-graft-derived SMCs near the anastomosis site in 1 transplanted carotid bifurcation, no SMCs originating from outside the local arterial segment were detected in healed plaques. Conclusions - Healing SMCs after atherosclerotic plaque disruption are derived entirely from the local arterial wall and not circulating progenitor cells in apoE(-/-) mice.
引用
收藏
页码:2053 / 2061
页数:9
相关论文
共 37 条
[1]   Simvastatin promotes atherosclerotic plaque stability in ApoE-deficient mice independently of lipid lowering [J].
Bea, F ;
Blessing, E ;
Bennett, B ;
Levitz, M ;
Wallace, EP ;
Rosenfeld, ME .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (11) :1832-1837
[2]   Smooth muscle cells in atherosclerosis originate from the local vessel wall and not circulating progenitor cells in ApoE knockout mice [J].
Bentzon, Jacob F. ;
Weile, Charlotte ;
Sondergaard, Claus S. ;
Hindkjaer, Johnny ;
Kassem, Moustapha ;
Falk, Erling .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (12) :2696-2702
[3]   Morphological predictors of arterial remodeling in coronary atherosclerosis [J].
Burke, AP ;
Kolodgie, FD ;
Farb, A ;
Weber, D ;
Virmani, R .
CIRCULATION, 2002, 105 (03) :297-303
[4]  
Burke AP, 2001, CIRCULATION, V103, P934
[5]   Spontaneous plaque rupture and secondary thrombosis in apolipoprotein E-deficient and LDL receptor-deficient mice [J].
Calara, F ;
Silvestre, M ;
Casanada, F ;
Yuan, N ;
Napoli, C ;
Palinski, W .
JOURNAL OF PATHOLOGY, 2001, 195 (02) :257-263
[6]   Smooth muscle cells in human coronary atherosclerosis can originate from cells administered at marrow transplantation [J].
Caplice, NM ;
Bunch, TJ ;
Stalboerger, PG ;
Wang, SH ;
Simper, D ;
Miller, DV ;
Russell, SJ ;
Litzow, MR ;
Edwards, WD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (08) :4754-4759
[7]   FACTORS INFLUENCING THE PRESENCE OR ABSENCE OF ACUTE CORONARY-ARTERY THROMBI IN SUDDEN ISCHEMIC DEATH [J].
DAVIES, MJ ;
BLAND, JM ;
HANGARTNER, JRW ;
ANGELINI, A ;
THOMAS, AC .
EUROPEAN HEART JOURNAL, 1989, 10 (03) :203-208
[8]   SM22α modulates vascular smooth muscle cell phenotype during atherogenesis [J].
Feil, S ;
Hofmann, F ;
Feil, R .
CIRCULATION RESEARCH, 2004, 94 (07) :863-865
[9]   SMOOTH-MUSCLE CELL ABUNDANCE AND FIBROBLAST GROWTH-FACTORS IN CORONARY LESIONS OF PATIENTS WITH NONFATAL UNSTABLE ANGINA - A CLUE TO THE MECHANISM OF TRANSFORMATION FROM THE STABLE TO THE UNSTABLE CLINICAL STATE [J].
FLUGELMAN, MY ;
VIRMANI, R ;
CORREA, R ;
YU, ZX ;
FARB, A ;
LEON, MB ;
ELAMI, A ;
FU, YM ;
CASSCELLS, W ;
EPSTEIN, SE .
CIRCULATION, 1993, 88 (06) :2493-2500
[10]   Vascular smooth muscle cell senescence in atherosclerosis [J].
Gorenne, Isabelle ;
Kavurma, Mary ;
Scott, Stephen ;
Bennett, Martin .
CARDIOVASCULAR RESEARCH, 2006, 72 (01) :9-17