Abstract | BACKGROUND: METHODS AND RESULTS:
Neointima formation was evaluated in PAI-1-deficient (PAI-1(-/-)) mice with perivascular electric or transluminal mechanical injury. PAI-1 deficiency improved vascular wound healing in both models: the cross-sectional neointimal area was 0.001+/-0.001 mm2 in PAI-1(+/+) and 0.016+/-0.008 mm2 in PAI-1(-/-) mice within 1 week after electric injury (P<.02) and 0.055+/-0.008 mm2 in PAI-1(+/+) and 0.126+/-0.006 mm2 in PAI-1(-/-) mice within 3 weeks after mechanical injury (P<.001). Proliferation of smooth muscle cells was not affected by PAI-1 deficiency. Topographic analysis of arterial wound healing after electric injury revealed that PAI-1(-/-) smooth muscle cells, originating from the uninjured borders, more rapidly migrated into the necrotic center of the arterial wound than wild-type smooth muscle cells. On the basis of immunostaining, PAI-1 expression was markedly upregulated during vascular wound healing. There were no genotypic differences in reendothelialization of the vascular wound. When PAI-1(-/-) mice were intravenously injected with replication-defective adenovirus expressing human PAI-1 (AdCMVPAI-1), plasma PAI-1 antigen levels increased in a dose-dependent fashion up to to 61+/-8 microg/mL with 2x10(9) plaque-forming units (pfu) virus. Luminal stenosis was 35+/-13% in control AdRR5-treated (2x10(9) pfu) and suppressed to 5+/-5% in AdCMVPAI-1-treated (6x10(8) pfu) PAI-1(-/-) mice (P<.002). CONCLUSIONS:
|
Authors | P Carmeliet, L Moons, R Lijnen, S Janssens, F Lupu, D Collen, R D Gerard |
Journal | Circulation
(Circulation)
Vol. 96
Issue 9
Pg. 3180-91
(Nov 04 1997)
ISSN: 0009-7322 [Print] United States |
PMID | 9386191
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
|
Chemical References |
- Plasminogen Activator Inhibitor 1
|
Topics |
- Adenoviridae
(genetics)
- Animals
- Cell Division
- Cell Movement
- Endothelium, Vascular
(cytology, physiology)
- Female
- Gene Targeting
- Gene Transfer Techniques
- Male
- Mice
- Mice, Inbred C57BL
- Muscle, Smooth, Vascular
(pathology)
- Plasminogen Activator Inhibitor 1
(analysis, genetics, physiology)
- Thrombosis
(prevention & control)
- Vascular Diseases
(prevention & control)
- Wound Healing
|