This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Cardiovascular disease is a leading cause of morbidity and mortality in Hawaii and the United States. Upon closer examination of cardiovascular disease death rates in Hawaii, Filipinos and Native Hawaiians have disproportionally higher mortality rates than the general population. Moreover, cardiovascular disease is responsible for a significant portion of the state health care costs from hospitalizations. Sudden cardiac death and acute heart attack often occur without warning and these complications are typically associated with a plaque rupture corresponding to advanced stages of coronary atherosclerotic heart disease. Recommendations in terms of diet and exercise have been developed to prevent atherosclerotic cardiovascular disease, but less effort has been made to aid patients who may be at risk for vulnerable plaque rupture. Coronary angiography has limitations because it does not allow for inspection of the vessel wall and can only determine narrowing of the vessel lumen. Intravascular ultrasound (IVUS) provides a two-dimensional cross-sectional view of the arterial wall and offers some ability to determine lumen and vessel areas. However, severe limitations exist in the classification of plaques. The high frequency signal may be confused with acoustic shadowing aspects. The mechanisms of plaque rupture are not well understood and no imaging modality currently exists which can robustly detect vulnerable plaques. Vulnerable plaques are characterized by a large lipid core with a thin and inflamed fibrous cap. Low endothelial shear stress from the surrounding blood flow can serve as stimulus for the progression and differentiation of an early fibroatheroma to a high-risk plaque. It has been hypothesized that the vasa vasorum, which supplies nutrients to the adventia, may serve as a conduit for white blood cells to migrate into the lining of the vessel wall. Subsequently, expansive vascular remodeling can occur within these plaques. The addition of molecular-imaging capabilities to IVUS probes would provide an improvement in detecting biomarkers for plaque rupture, such as neovascularization and inflammation. Targeted ultrasound contrast agents are encapsulated microbubbles with attached ligands that allow them to bind to specific diseased sites. The center frequency of IVUS probes (35-50 MHz) is much higher than conventional diagnostic ultrasound systems. During the previous year we utilized excised coronary arteries from patients. Now the work has been extended to an animal model of plaque in mice.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Research Centers in Minority Institutions Award (G12)
Project #
2G12RR003061-26
Application #
8357170
Study Section
Special Emphasis Panel (ZRR1-RI-B (02))
Project Start
2011-09-16
Project End
2012-07-31
Budget Start
2011-09-16
Budget End
2012-07-31
Support Year
26
Fiscal Year
2011
Total Cost
$161,830
Indirect Cost
Name
University of Hawaii
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
965088057
City
Honolulu
State
HI
Country
United States
Zip Code
96822
Priemer, David S; Wang, Mingsheng; Zhang, Shaobo et al. (2018) Small-cell Carcinomas of the Urinary Bladder and Prostate: TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma. Eur Urol Focus 4:880-888
Marciel, Michael P; Rose, Aaron H; Martinez, Verena et al. (2018) Calpain-2 inhibitor treatment preferentially reduces tumor progression for human colon cancer cells expressing highest levels of this enzyme. Cancer Med 7:175-183
Marciel, Michael P; Khadka, Vedbar S; Deng, Youpeng et al. (2018) Selenoprotein K deficiency inhibits melanoma by reducing calcium flux required for tumor growth and metastasis. Oncotarget 9:13407-13422
Baumer, Yvonne; McCurdy, Sara; Weatherby, Tina M et al. (2017) Hyperlipidemia-induced cholesterol crystal production by endothelial cells promotes atherogenesis. Nat Commun 8:1129
Wilcox, Christie L; Headlam, Jasmine L; Doyle, Thomas K et al. (2017) Assessing the Efficacy of First-Aid Measures in Physalia sp. Envenomation, Using Solution- and Blood Agarose-Based Models. Toxins (Basel) 9:
Yanagihara, Angel Anne; Wilcox, Christie L (2017) Cubozoan Sting-Site Seawater Rinse, Scraping, and Ice Can Increase Venom Load: Upending Current First Aid Recommendations. Toxins (Basel) 9:
Chang, Linda; Løhaugen, Gro C; Andres, Tamara et al. (2017) Adaptive working memory training improved brain function in human immunodeficiency virus-seropositive patients. Ann Neurol 81:17-34
Doyle, Thomas K; Headlam, Jasmine L; Wilcox, Christie L et al. (2017) Evaluation of Cyanea capillata Sting Management Protocols Using Ex Vivo and In Vitro Envenomation Models. Toxins (Basel) 9:
Pomozi, Viola; Brampton, Christopher; van de Wetering, Koen et al. (2017) Pyrophosphate Supplementation Prevents Chronic and Acute Calcification in ABCC6-Deficient Mice. Am J Pathol 187:1258-1272
Pomozi, Viola; Brampton, Christopher; Szeri, Flóra et al. (2017) Functional Rescue of ABCC6 Deficiency by 4-Phenylbutyrate Therapy Reduces Dystrophic Calcification in Abcc6-/- Mice. J Invest Dermatol 137:595-602

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