Neointima formation and thrombosis after vascular injury in transgenic mice overexpressing plasminogen activator inhibitor-1 (PAI-1)

被引:23
作者
Lijnen, HR [1 ]
Van Hoef, B [1 ]
Umans, K [1 ]
Collen, D [1 ]
机构
[1] Univ Louvain, Ctr Mol & Vasc Biol, B-3000 Louvain, Belgium
关键词
neointima; PAI-1; restenosis; transgenic mice;
D O I
10.1111/j.1538-7836.2003.00533.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The controversial role of plasminogen activator inhibitor-1 (PAI-1) in neointima formation and restenosis was studied with the use of a vascular injury model in transgenic mice overexpressing murine PAI-1 (PAI-1 Tg) and in wild-type (WT) controls. Despite the high circulating PAI-1 levels in the PAI-1 Tg mice (52+/-9.8 ng mL(-1) vs. 0.76+/-0.17 ng mL(-1) in WT mice), no significant fibrin deposition was observed in non-injured femoral arteries of 8- to 12-week-old mice. Two weeks after severe electric injury, extensive and comparable fibrin deposition was observed in both genotypes, despite a significantly reduced in situ fibrinolytic activity in arterial sections of the PAI-1 Tg mice. The neointimal and medial areas were similar in WT and PAI-1 Tg mice, resulting in comparable intima/media ratios (e.g. 0.94+/-0.25 and 1.04+/-0.17 at the center of the injury). Nuclear cell counts in cross-sectional areas of the neointima of the injured region were also comparable in arteries from WT and PAI-1 Tg mice (224+/-63, 233+/-20), and the distribution pattern of a-actin-positive smooth muscle cells was similar. These findings indicate that in a vascular injury model that induces extensive and persistent fibrin deposition in femoral arteries of mice, overexpression of PAI-1 does not affect neointima formation.
引用
收藏
页码:16 / 22
页数:7
相关论文
共 34 条
  • [1] Burke AP, 2001, CIRCULATION, V103, P934
  • [2] Carmeliet P, 1997, AM J PATHOL, V150, P761
  • [3] Receptor-independent role of urokinase-type plasminogen activator in pericellular plasmin and matrix metalloproteinase proteolysis during vascular wound healing in mice
    Carmeliet, P
    Moons, L
    Dewerchin, M
    Rosenberg, S
    Herbert, JM
    Lupu, F
    Collen, D
    [J]. JOURNAL OF CELL BIOLOGY, 1998, 140 (01) : 233 - 245
  • [4] Carmeliet P, 1997, CIRC RES, V81, P829
  • [5] Inhibitory role of plasminogen activator inhibitor-1 in arterial wound healing and neointima formation - A gene targeting and gene transfer study in mice
    Carmeliet, P
    Moons, L
    Lijnen, HR
    Janssens, S
    Lupu, F
    Collen, D
    Gerard, RD
    [J]. CIRCULATION, 1997, 96 (09) : 3180 - 3191
  • [6] Carmeliet P, 2000, J PATHOL, V190, P387
  • [7] Plasminogen activator inhibitor 1 and vitronectin protect against stenosis in a murine carotid artery ligation model
    de Waard, V
    Arkenbout, EK
    Carmeliet, P
    Lindner, V
    Pannekoek, H
    [J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2002, 22 (12) : 1978 - 1983
  • [8] DECLERCK PJ, 1995, THROMB HAEMOSTASIS, V74, P1305
  • [9] DECLERCK PJ, 1988, J BIOL CHEM, V263, P15454
  • [10] Plasminogen activator inhibitor type I increases neointima formation in balloon-injured rat carotid arteries
    DeYoung, MB
    Tom, C
    Dichek, DA
    [J]. CIRCULATION, 2001, 104 (16) : 1972 - 1977