Plasminogen activation: a mediator of vascular smooth muscle cell apoptosis in atherosclerotic plaques.
BACKGROUND
Apoptosis of vascular cells is considered to be a major determinant of atherosclerotic plaque vulnerability and potential rupture. Plasmin can be generated in atherosclerotic plaques and recent in vitro data suggest that plasminogen activation may trigger vascular smooth muscle cell (VSMC) apoptosis.


OBJECTIVE
To determine whether plasminogen activation may induce aortic VSMC apoptosis ex vivo and in vivo.


RESULTS
Mice with single or combined deficiencies of apolipoprotein E (ApoE) and plasminogen activator inhibitor-1 (PAI-1) were used. Ex vivo incubation with plasminogen of isolated aortic tunica media from PAI-1-deficient mice induced plasminogen activation and VSMC apoptosis, which was inhibited by alpha2-antiplasmin. In vivo, levels of plasmin, active caspase 3 and VSMC apoptotic index were significantly higher in atherosclerotic aortas from mice with combined ApoE and PAI-1 deficiencies than in those from littermates with single ApoE deficiency. A parallel decrease in VSMC density was observed.


CONCLUSIONS
These data strongly suggest that plasminogen activation may contribute to VSMC apoptosis in atherosclerotic plaques.
Rossignol
P
P
Center for Molecular and Vascular Biology, K.U. Leuven, Belgium.
Luttun
A
A
Martin-Ventura
J L
JL
Lupu
F
F
Carmeliet
P
P
Collen
D
D
Anglès-Cano
E
E
Lijnen
H R
HR
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D005341:Fibrinolysin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D010958:Plasminogen / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
D001057:Apolipoproteins E; D017395:Plasminogen Activator Inhibitor 1; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D005341:Fibrinolysin