Inhibitor of apoptosis protein survivin regulates vascular injury.
Survivin (also termed Birc5) belongs to the family of genes known as inhibitors of apoptosis, and it has been implicated in both prevention of cell death and control of mitosis. The survivin pathway is exploited in cancer, but its potential role in vascular injury is unknown. Here, we show that balloon-mediated arterial injury in rabbits resulted in expression of survivin in vascular cells. Serum or PDGF-AB stimulated survivin expression in cultured smooth-muscle cells (SMCs), which suppressed apoptosis and prevented caspase activation. Adenoviral delivery of a phosphorylation-defective survivin mutant reversed the cytoprotective effect of PDGF in SMCs without affecting mitotic progression, suppressed neointimal formation in wire-injured mouse femoral arteries, and induced vascular cell apoptosis in vivo. These data identify survivin as a critical regulator of SMC apoptosis after acute vascular injury. Disrupting the survivin pathway may provide a novel therapy to limit pathological vessel-wall remodeling.
Blanc-Brude
Olivier P
OP
Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, Connecticut, USA.
Yu
Jun
J
Simosa
Hector
H
Conte
Michael S
MS
Sessa
William C
WC
Altieri
Dario C
DC
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D001158:Arteries / Q000293:injuries* / Q000378:metabolism; D002404:Catheterization / Q000009:adverse effects; D002478:Cells, Cultured; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins; D009131:Muscle, Smooth, Vascular / Q000293:injuries* / Q000378:metabolism*; D009154:Mutation; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor / Q000378:metabolism / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D000077022:Survivin; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D010982:Platelet-Derived Growth Factor; D000077022:Survivin; C095477:platelet-derived growth factor AB