Localization of c-Myb and induction of apoptosis by antisense oligonucleotide c-myb after angioplasty of porcine coronary arteries

D. L. Lambert, N. Malik, L. Shepherd, J. Gunn, S. E. Francis, A. King, D. C. Crossman, D. C. Cumberland, Cathy M. Holt, CM. Holt

    Research output: Contribution to journalArticlepeer-review

    Abstract

    Previous studies have shown that inhibition of the proto-oncogene c-myb inhibits neointimal formation in various animal models. However, the temporal and spatial expression of c-Myb in the vessel wall after injury is not known, and the mechanism of action of antisense oligonucleotide (AS-ODN-c-myb) inhibition remains unclear. One potential effect of cell cycle dysregulation by inhibition of c-myb is an increase in the rates of apoptosis. In this study, c-Myb expression after percutaneous transluminal coronary angioplasty (PTCA) injury and induction of apoptosis after AS-ODN-c-myb treatment were determined. Immunohistochemistry and cellular phenotyping were used to localize c-Myb expression in porcine coronary arteries at various time intervals after PTCA. In vitro, the effects of AS-ODN-c-myb on the apoptosis of porcine vascular smooth muscle cells (PVSMCs) and endothelial cells were determined by using a cell-death ELISA and time-lapse video microscopy. In vivo, local delivery of AS-ODN-c-myb was performed after PTCA of pig coronary arteries, and apoptosis was quantified at 6 hours, c-Myb is induced in pig coronary arteries after angioplasty, with maximal expression in inflammatory cells at 18 hours and in vascular smooth muscle cells at 3 to 7 days. In vitro, AS-ODN-c-myb enhanced PVSMCs (6.8±0.8% [P=
    Original languageEnglish
    Pages (from-to)1727-1732
    Number of pages5
    JournalArteriosclerosis, Thrombosis, and Vascular Biology
    Volume21
    Issue number11
    DOIs
    Publication statusPublished - 2001

    Keywords

    • Angioplasty
    • Antisense
    • Apoptosis
    • Proto-oncogenes

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