Human ApoA-I transfer attenuates transplant arteriosclerosis via enhanced incorporation of bone marrow-derived endothelial progenitor cells

被引:72
作者
Feng, Yingmei [1 ]
Jacobs, Frank [1 ]
Van Craeyveld, Eline [1 ]
Brunaud, Christine [1 ]
Snoeys, Jan [1 ]
Tjwa, Marc [2 ]
Van Linthout, Sophie [3 ]
De Geest, Bart [1 ]
机构
[1] Katholieke Univ Leuven, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium
[2] Katholieke Univ Leuven VIB, Ctr Transgene Technol & Gene Thrrapy, Louvain, Belgium
[3] Univ Med Berlin, Charite, Dept Cardiol, Berlin, Germany
关键词
high density lipoproteins; apolipoprotein A-I; hypercholesterolemia; endothelial progenitor cells; transplant arteriosclerosis;
D O I
10.1161/ATVBAHA.107.158741
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Objective-Transplant arteriosclerosis is the leading cause of graft failure and death in patients with heart transplantation. Endothelial progenitor cells (EPCs) contribute to endothelial regeneration in allografts. We investigated whether increased HDL cholesterol induced by adenoviral human apoA-I (AdA-I) transfer increases number and function of EPCs, promotes incorporation of EPCs in Balb/c allografts transplanted paratopically in C57BL/6 ApoE(-/-) mice, and attenuates transplant arteriosclerosis. Methods and Results-EPC number in ApoE(-/-) mice was increased after AdA-I transfer as evidenced by 1.5-fold (P < 0.01) higher Flk-1 Sca-1-positive cells and 1.4-fold (P < 0.01) higher DiI-acLDL isolectin-positive spleen cells. In addition, HDL enhanced EPC function in vitro. Incorporation of bone marrow-derived EPCs was 5.8-fold (P < 0.01) higher at day 21 after transplantation in AdA-I-treated apoE(-/-) mice compared with control mice. Enhanced endothelial regeneration in AdA-I-treated apoE(-/-) mice as evidenced by a 2.6-fold (P < 0.01) increase of CD31-positive endothelial cells resulted in a 1.4-fold (P < 0.059) reduction of neointima and a 3.9-fold (P < 0.01) increase of luminal area. Conclusion-Human apoA-I transfer increases the number of circulating EPCs, enhances their incorporation into allografts, promotes endothelial regeneration, and attenuates neointima formation in a murine model of transplant arteriosclerosis.
引用
收藏
页码:278 / 283
页数:6
相关论文
共 43 条
[31]   Arterial remodeling in the left coronary system - The role of high-density lipoprotein cholesterol [J].
Taylor, AJ ;
Burke, AP ;
Farb, A ;
Yousefi, P ;
Malcom, GT ;
Smialek, J ;
Virmani, R .
JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 1999, 34 (03) :760-767
[32]   Human endothelial progenitor exhibit impaired proliferation, cells from type II diabetics adhesion, and incorporation into vascular structures [J].
Tepper, OM ;
Galiano, RD ;
Capla, JM ;
Kalka, C ;
Gagne, PJ ;
Jacobowitz, GR ;
Levine, JP ;
Gurtner, GC .
CIRCULATION, 2002, 106 (22) :2781-2786
[33]   Role of NO in flow-induced remodeling of the rabbit common carotid artery [J].
Tronc, F ;
Wassef, M ;
Esposito, B ;
Henrion, D ;
Glagov, S ;
Tedgui, A .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 1996, 16 (10) :1256-1262
[34]   High-density lipoproteins enhance progenitor-mediated endothelium repair in mice [J].
Tso, C ;
Martinic, G ;
Fan, WH ;
Rogers, C ;
Rye, KA ;
Barter, PJ .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2006, 26 (05) :1144-1149
[35]   Persistent hepatic expression of human apo A-I after transfer with a helper-virus independent adenoviral vector [J].
Van Linthout, S ;
Lusky, M ;
Collen, D ;
De Geest, B .
GENE THERAPY, 2002, 9 (22) :1520-1528
[36]   Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease [J].
Vasa, M ;
Fichtlscherer, S ;
Aicher, A ;
Adler, K ;
Urbich, C ;
Martin, H ;
Zeiher, AM ;
Dimmeler, S .
CIRCULATION RESEARCH, 2001, 89 (01) :E1-E7
[37]   High-density lipoproteins neutralize C-reactive protein proinflammatory activity [J].
Wadham, C ;
Albanese, N ;
Roberts, J ;
Wang, LJ ;
Bagley, CJ ;
Gamble, JR ;
Rye, KA ;
Barter, PJ ;
Vadas, MA ;
Xia, P .
CIRCULATION, 2004, 109 (17) :2116-2122
[38]   Impaired CXCR4 signaling contributes to the reduced neovascularization capacity of endothelial progenitor cells from patients with coronary artery disease [J].
Walter, DH ;
Haendeler, J ;
Reinhold, J ;
Rochwalsky, U ;
Seeger, F ;
Honold, J ;
Hoffmann, J ;
Urbich, C ;
Lehmann, R ;
Seisdesdos, FA ;
Aicher, A ;
Heeschen, C ;
Fichtlscherer, S ;
Zeiher, AM ;
Dimmeler, S .
CIRCULATION RESEARCH, 2005, 97 (11) :1142-1151
[39]   Cardiac allograft vasculopathy - A review [J].
Weis, M ;
vonScheidt, W .
CIRCULATION, 1997, 96 (06) :2069-2077
[40]   Intravenous transfusion of endothelial progenitor cells reduces neointima formation after vascular injury [J].
Werner, N ;
Junk, S ;
Laufs, U ;
Link, A ;
Walenta, K ;
Böhm, M ;
Nickenig, G .
CIRCULATION RESEARCH, 2003, 93 (02) :E17-E24