title: Apolipoprotein (a) impairs endothelial progenitor cell-mediated angiogenesis.
abstract: Improvement of blood flow and promotion of angiogenesis are important therapeutic measures for the treatment of ischemic peripheral vascular diseases. Since apolipoprotein (a) (apo (a)) is a glycoprotein with repetitive kringle domains exhibiting 75% to 98% structural homology with plasminogen (Plg), apo (a) may also have a negative effect on endothelial progenitor cell (EPC)-induced angiogenesis through Plg-like inhibitory effects on EPC proliferation, adhesion, migration, and angiogenesis. To evaluate the effect of apo (a) on EPCs-induced angiogenesis, EPCs were isolated from the bone marrow of apo (a) transgenic mice, wild-type litter mates, and normal mice. These cells were cultured without or with apo (a) before transplantation. Hindlimb ischemia models were surgically induced in mice, which then received an intravenous injection of 3×10(5) EPCs. At 3, 7, and 14 days post EPC transplantation, the adhesion, migration abilities, and capillary density in calf muscles were assessed. Results indicate that apo (a) significantly reduced the adhesion and migration abilities of EPCs. Furthermore, the tubule-like formation of EPCs on Matrigel gels was damaged. In vivo experiments showed the homing of EPCs to ischemic peripheral vascular, and the number of capillary vessels decreased significantly in apo(a) transgenic mice. This study demonstrated that apo (a) could attenuate the adhesion, migration, and homing abilities of EPCs and could impair the angiogenesis ability of EPCs.
authors.affiliation: Key Laboratory for Arteriosclerology of Hunan Province, Institute of Cardiovascular Disease, University of South China, Hengyang City, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Wang
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.forename: Zhongyi
authors.initials: Z
authors.lastname: Tong
authors.forename: Guohua
authors.initials: G
authors.lastname: Li
authors.forename: Zhanzhi
authors.initials: Z
authors.lastname: Zhao
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhao
authors.forename: Fengtao
authors.initials: F
authors.lastname: Liu
authors.forename: Xiaolong
authors.initials: X
authors.lastname: Lin
authors.forename: Zuo
authors.initials: Z
authors.lastname: Wang
authors.forename: Zhisheng
authors.initials: Z
authors.lastname: Jiang
mesh_terms: D000818:Animals; D053241:Apoprotein(a) / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002465:Cell Movement / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D015536:Down-Regulation / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000235:genetics* / Q000502:physiology; D013234:Stem Cells / Q000378:metabolism / Q000502:physiology*
chemical_list: D053241:Apoprotein(a)