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Ribonucleotide Reductase Inhibitors for Restenosis

Mutchler, Megan Marie
http://rave.ohiolink.edu/etdc/view?acc_num=osu1211423147

Abstract Details

2008, Master of Science, Ohio State University, Pathology.
Percutaneous transluminal coronary angioplasty (PTCA) has greatly benefited patients with occluded coronary arteries, but its benefits have been undermined by a high incidence of restenosis. The introduction of coronary stents has significantly improved the short and long term outcome but restenosis still occurs in approximately 15-30 % of patients within 6 months. Research efforts are now being directed toward combination stenting and drug delivery. Among the therapeutic targets being pursued are agents which can impede smooth muscle cell (SMC) migration and proliferation as these processes are critical components of restenosis injury. We propose that inhibiting the conversion of ribonucleotides to deoxyribonucleotides will impede cell proliferation and as such limit the degree of restenosis. Therefore, we tested whether the potent Ribonucleotide Reductase (RR) inhibitors, Didox and Imidate, can limit the neointimal proliferation associated with restenosis using rat, rabbit and porcine models of vascular injury. Results demonstrated that systemic administration of the RR inhibitors Didox, Imidate and Hydroxyurea significantly reduced intimal thickening, intima/media ratio and lumen loss. Results from cell proliferation studies suggest that the mechanism of protection is inhibition of SMC proliferation and decreased number of circulating leukocytes. These results suggest that inhibition of Ribonucleotide Reductase may provide a potent strategy to prevent post PTCA restenosis.
James Waldman, Phd (Advisor)
Arturo Cardounel, Phd (Committee Member)
Guanglong He, Phd (Committee Member)
77 p.
Pathology
restenosis; atherosclerosis; percutaneous balloon angioplasty; stent

Recommended Citations

Citations

  • Mutchler, M. M. (2008). Ribonucleotide Reductase Inhibitors for Restenosis [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1211423147

    APA Style (7th edition)

  • Mutchler, Megan. Ribonucleotide Reductase Inhibitors for Restenosis. 2008. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1211423147.

    MLA Style (8th edition)

  • Mutchler, Megan. "Ribonucleotide Reductase Inhibitors for Restenosis." Master's thesis, Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=osu1211423147

    Chicago Manual of Style (17th edition)

osu1211423147
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© 2008, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.