The Vascular Imaging Core (Core Unit B) will be primarily responsible for the phenotyping of vascular structure in humans with metabolic syndrome. The principal functions of the Vascular Imaging Core Laboratory are to: 1) perform and analyze all vascular tests, including tests of vascular structure (by use of ultrasound, multidetector CT [MDCT] and/or magnetic resonance imaging [MRI]), and 24-hour blood pressure monitoring, 2) collect, process and store blood samples for all cardiovascular and inflammatory serum markers and genetic analyses, 3) provide a project-wide cardiovascular phenotype database, and 4) facilitate comparison and correlation of data, including the correlation of cardiovascular tests with clinical phenotypes and genotypes. In addition to performing the clinically-validated tests of vascular structure mentioned above, we propose to develop and test novel image-based phenotyping methods based on molecular imaging and targeted therapeutics with nanoparticles that could lead to earlier diagnosis and treatment for patients with metabolic syndrome. Accordingly, we will pursue multiple complementary diagnostic approaches to define optimally sensitive and specific methods for characterizing the very earliest manifestations of vascular disease in metabolic syndrome, particularly the vulnerable and unstable plaque. We will develop unique therapeutic formulations that can be site-targeted to unstable or vulnerable plaques with local or systemic delivery. We will employ a new class of nanotechnologies developed in our laboratory as molecular contrast agents for ultrasound and magnetic resonance imaging in view of their wide availability and power as screening tools. The nanotechnologies also serve as drug carriers that can deposit large quantities of lipophilic agents into the cell cytoplasm directly through a process called """"""""contact facilitated drug delivery"""""""" now patent-pending in our laboratory. Interfacing clinically-validated vascular tests with evolving nanotechnology approaches has the potential to transform the care of people with the metabolic syndrome through the development of novel drug delivery and vascular phenotyping techniques.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL083762-05
Application #
8072197
Study Section
Special Emphasis Panel (ZHL1)
Project Start
Project End
2013-04-30
Budget Start
2010-05-01
Budget End
2013-04-30
Support Year
5
Fiscal Year
2010
Total Cost
$390,259
Indirect Cost
Name
Washington University
Department
Type
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Jamis-Dow, Carlos A; Barbier, George H; Watkins, Mary P et al. (2014) Bicuspid Pulmonic Valve and Pulmonary Artery Aneurysm. Cardiol Res 5:83-84
Airhart, Nathan; Brownstein, Bernard H; Cobb, J Perren et al. (2014) Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin. J Vasc Surg 60:1033-41; discussion 1041-2
Thatcher, Sean E; Zhang, Xuan; Howatt, Deborah A et al. (2014) Angiotensin-converting enzyme 2 decreases formation and severity of angiotensin II-induced abdominal aortic aneurysms. Arterioscler Thromb Vasc Biol 34:2617-23
Jin, Jianping; Arif, Batool; Garcia-Fernandez, Francisca et al. (2012) Novel mechanism of aortic aneurysm development in mice associated with smoking and leukocytes. Arterioscler Thromb Vasc Biol 32:2901-9
Razani, Babak; Feng, Chu; Coleman, Trey et al. (2012) Autophagy links inflammasomes to atherosclerotic progression. Cell Metab 15:534-44
Jiang, Xuntian; Sidhu, Rohini; Porter, Forbes D et al. (2011) A sensitive and specific LC-MS/MS method for rapid diagnosis of Niemann-Pick C1 disease from human plasma. J Lipid Res 52:1435-45
Wei, Xiaochao; Schneider, Jochen G; Shenouda, Sherene M et al. (2011) De novo lipogenesis maintains vascular homeostasis through endothelial nitric-oxide synthase (eNOS) palmitoylation. J Biol Chem 286:2933-45
Razani, Babak; Zhang, Haixia; Schulze, P Christian et al. (2011) Fatty acid synthase modulates homeostatic responses to myocardial stress. J Biol Chem 286:30949-61
Porter, Forbes D; Scherrer, David E; Lanier, Michael H et al. (2010) Cholesterol oxidation products are sensitive and specific blood-based biomarkers for Niemann-Pick C1 disease. Sci Transl Med 2:56ra81
Marquart, Tyler J; Allen, Ryan M; Ory, Daniel S et al. (2010) miR-33 links SREBP-2 induction to repression of sterol transporters. Proc Natl Acad Sci U S A 107:12228-32

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