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Development of cardiovascular nanodevices for the detection of vulnerable plaque

Kebbel, Andrew D.
http://rave.ohiolink.edu/etdc/view?acc_num=osu1185478006

Abstract Details

2006, Master of Science, Ohio State University, Biomedical Engineering.
The primary health problem facing Americans today is cardiovascular disease. Cardiovascular disease results in more deaths every year than the next four leading causes of death combined (cancer, respiratory diseases, accidents, and diabetes). A particularly frightening fact is that about two thirds of unexpected cardiac deaths occur without manifestation of symptoms related to heart disease. Many of these unexpected deaths occur when a vulnerable plaque ruptures, exposing prothrombotic material to the circulation, often resulting in complete and catastrophic occlusion of the blood vessel. Current medical imaging modalities (CT, MRI, angiography, etc.) can identify narrowing of the arteries, but they are all limited in the information they provide regarding the vulnerability of the plaque. This work will present results aimed at identifying novel targeting agents to vulnerable plaque with the goal of developing a targeted contrast-enhancing nanodevice that can be used to detect vulnerable plaque before rupture. Phage displayed peptide libraries were used to probe the molecular architecture of the Watanabe heritable hyperlipidemic (WHHL) rabbit animal model of atherosclerosis. Over 200 novel peptide sequences were isolated, of which 45 were selected for synthesis and further assaying. Binding assays were conducted in several systems: lipid-loaded human aortic endothelial cells (HAECs), WHHL rabbits, New Zealand white (NZW) rabbits (a non-diseased control animal), and ApoE knockout mice (murine model of atherosclerosis). One peptide in particular, TQTPIKHHLLKE (peptide 9), was found to consistently bind plaque in the WHHL model in a dose-dependent manner. Furthermore, binding of peptide 9 to the NZW model was seen as light background binding, which did not increase with increased concentration of peptide. This indicates that peptide 9 is a potential plaque-targeting agent and should be used in future work to develop targeted image-contrast nanodevices to atherosclerotic plaque. Results for all other peptides are presented and discussed as well. Experiments to isolate the protein to which peptide 9 binds were unsuccessful, but recommendations are made that will improve the likelihood of isolating the protein.
Stephen Lee (Advisor)
90 p.

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Citations

  • Kebbel, A. D. (2006). Development of cardiovascular nanodevices for the detection of vulnerable plaque [Master's thesis, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1185478006

    APA Style (7th edition)

  • Kebbel, Andrew. Development of cardiovascular nanodevices for the detection of vulnerable plaque. 2006. Ohio State University, Master's thesis. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1185478006.

    MLA Style (8th edition)

  • Kebbel, Andrew. "Development of cardiovascular nanodevices for the detection of vulnerable plaque." Master's thesis, Ohio State University, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=osu1185478006

    Chicago Manual of Style (17th edition)

osu1185478006
1,270
© 2006, all rights reserved.
This open access ETD is published by The Ohio State University and OhioLINK.