title: Changes in vessel wall plasminogen activator activity and smooth muscle cell proliferation and activation after arterial injury.
abstract: OBJECTIVE
  The aim was to examine changes in vessel wall fibrinolytic activity following angioplasty and to assess any relationship to changes in smooth muscle cell proliferation and activation.
  
  
  METHODS
  Balloon angioplasty was performed to the iliac arteries of New Zealand White rabbits and vessel wall changes assessed at 2 h, 1 d, 7 d, 14 d, and 1 month postprocedure. Tissue-type (tPA) and urokinase-type (uPA) plasminogen activator activity was assessed using chromogenic substrate assays, while smooth muscle cell proliferation and activation was monitored using expression of proliferating cell nuclear antigen (PCNA) and of basic fibroblast growth factor (bFGF) respectively.
  
  
  RESULTS
  Intimal thickening progressively increased up to 1 month. uPA activity increased at 2 h [1.94(SEM 0.19) v 1.59(0.05) U.mg-1 tissue for control vessels, P = 0.03], remained increased at 24 h, but by 7 d had decreased to below control levels and remained low. In contrast, tPA activity fell significantly at 2 h [0.9(0.3) v 1.96(0.13) micrograms.mg-1 tissue for control vessels, P = 0.03], remained low at 24 h, but by 7 d had reverted back to control levels [2.19(0.39) micrograms.mg-1]. PCNA positivity of the media increased at day 1, reached maximum on day 7 [16.9(5.1)% positively staining cells] before returning to baseline by 1 month. PCNA positivity of the intima first evident at day 7 [0.7(0.3)%], reached a maximum at day 14 [4.1(0.4)%]. bFGF expression increased early at 2 h [mean(SE) positively staining cells: 15.7(5.3)% v 11.2(4.8)% for control vessels] and continued to increase, reaching a maximum in the media at day 7 [59(8.6)%] and in the intima at day 14 [57.5(5.7)%].
  
  
  CONCLUSIONS
  Balloon injury produced an initial fall in tPA and rise in uPA activity. tPA increased back to control levels by 7 d, while uPA fell to below control levels at 7 d and 1 month. This would be compatible with a mechanism whereby acute injury suppressed tPA and upregulated uPA activity, with increased tPA activity acting as a marker for vessel repair.
authors.affiliation: Academic Department of Cardiology, Glenfield Hospital, Leicester, United Kingdom.
authors.forename: R S
authors.initials: RS
authors.lastname: More
authors.forename: M J
authors.initials: MJ
authors.lastname: Underwood
authors.forename: M J
authors.initials: MJ
authors.lastname: Brack
authors.forename: D P
authors.initials: DP
authors.lastname: de Bono
authors.forename: A H
authors.initials: AH
authors.lastname: Gershlick
mesh_terms: D000800:Angioplasty, Balloon; D000818:Animals; D002455:Cell Division / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000473:pathology; D005342:Fibrinolysis / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000032:analysis; D007083:Iliac Artery / Q000201:enzymology / Q000293:injuries*; D007124:Immunoenzyme Techniques; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D010960:Plasminogen Activators / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D011817:Rabbits; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
chemical_list: D018809:Proliferating Cell Nuclear Antigen; D016222:Fibroblast Growth Factor 2; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator