Abstract

? For decades, the association of angiogenesis and atherosclerosis has been well known. Expansion of the network of small capillaries that perfuse the wall of larger blood vessels, the vasa vasorum, is recognized in diseases of chronic inflammation (e.g., atherosclerosis) and injury (e.g., angioplasty). Many hypothesize that the inward penetration of neo-vasculature within the arterial wall promotes plaque growth, intra-plaque hemorrhage, and lesion instability. This cascade of events precipitates intra-luminal thrombosis and thromboembolism, which are the proximate causes of myocardial infarction and stroke. Thus, plaque angiogenesis may be the linchpin pathology for the acute complications of atherosclerosis. ? ? The ultimate aims of this proposal involve magnetic resonance molecular imaging of plaque neo-vasculature in conjunction with local anti-angiogenesis therapy. Specifically, alpha v beta 3 -targeted paramagnetic nanoparticles will be used to spatially localize and quantify early atherosclerotic burdens in hyperlipidemic New Zealand White rabbits and to deliver fumagillin to elicit a marked antiangiogenic effect. The project will explore the potential of HMG-Coa reductase inhibitors to sustain the acute """"""""atherolytic"""""""" response of targeted fumagillin therapy and will evaluate the safety, pharmacokinetics and pharmacodynamics of this technology. This novel application of molecular imaging and targeted drug delivery could serve as part of a primary prevention strategy to diagnose, treat, and monitor early atherosclerosis. ? ? ?

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL078631-02
Application #
6950739
Study Section
Special Emphasis Panel (ZHL1-CSR-K (S1))
Program Officer
Buxton, Denis B
Project Start
2004-09-22
Project End
2008-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$379,850
Indirect Cost

  Institution

Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130

  Publications

Wang, Kezheng; Pan, Dipanjan; Schmieder, Anne H et al. (2015) Atherosclerotic neovasculature MR imaging with mixed manganese-gadolinium nanocolloids in hyperlipidemic rabbits. Nanomedicine 11:569-78
Pan, Dipanjan; Cai, Xin; Yalaz, Ceren et al. (2012) Photoacoustic sentinel lymph node imaging with self-assembled copper neodecanoate nanoparticles. ACS Nano 6:1260-7
Pan, Dipanjan; Sanyal, Nibedita; Schmieder, Anne H et al. (2012) Antiangiogenic nanotherapy with lipase-labile Sn-2 fumagillin prodrug. Nanomedicine (Lond) 7:1507-19
Zhang, Lingbo; Wang, Kezheng; Zhao, Falin et al. (2012) Near infrared imaging of EGFR of oral squamous cell carcinoma in mice administered arsenic trioxide. PLoS One 7:e46255
Cai, Kejia; Caruthers, Shelton D; Huang, Wenjing et al. (2010) MR molecular imaging of aortic angiogenesis. JACC Cardiovasc Imaging 3:824-32
Lanza, G M; Winter, P M; Caruthers, S D et al. (2010) Theragnostics for tumor and plaque angiogenesis with perfluorocarbon nanoemulsions. Angiogenesis 13:189-202
Caruthers, S D; Winter, P M; Wickline, S A et al. (2010) MR molecular imaging of angiogenesis using targeted perfluorocarbon nanoparticles. Medicamundi 54:5-13
Pan, Dipanjan; Caruthers, Shelton D; Chen, Junjie et al. (2010) Nanomedicine strategies for molecular targets with MRI and optical imaging. Future Med Chem 2:471-90
Kaneda, Megan M; Caruthers, Shelton; Lanza, Gregory M et al. (2009) Perfluorocarbon nanoemulsions for quantitative molecular imaging and targeted therapeutics. Ann Biomed Eng 37:1922-33
Southworth, Richard; Kaneda, Megan; Chen, Junjie et al. (2009) Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by (19)F NMR of VCAM-1 targeted nanobeacons. Nanomedicine 5:359-67

Showing the most recent 10 out of 31 publications