Novel strategies for promoting angiogenesis are being developed to treat patients with chronic coronary artery disease or peripheral vascular disease who are not amenable to revascularization. The overall purpose of this proposal is to apply novel contrast-enhanced ultrasound techniques to non-invasively assess molecular and cellular processes that are thought to contribute to angiogenesis. Contrast-enhanced ultrasound has been used to non-invasively assess microvascular perfusion in ischemic heart and limb disease, and can provide information on blood flow and blood volume in the different vascular compartments. Novel microbubble contrast agents targeted to either alpha-v integrins or to activate leukocytes have been developed to non-invasively image integrin expression and inflammation.
The first aim will be to apply these techniques to spatially and temporally characterize the relation between alpha-v integrin expression, the cellular inflammatory response, and perfusion in different models of angiogenesis. First, we will study these events in a matrigel model of angiogenesis in mice. Second, we will study the relation between alpha-v integrin expression, inflammation, and perfusion in a model of endogenous angiogenesis that occurs in response to ischemia produced by severe peripheral vascular disease in rats.
The second aim of this proposal is to determine how patterns of alpha-v integrin expression and inflammation are influenced by pro-angiogenic therapy with FGF-2 in the setting of severe peripheral vascular disease in rats. Successful completion of these studies will provide information that will likely be important for developing new proangiogenic strategies. These studies will also validate the potential use of targeted contrast ultrasound for non-invasively evaluating new pro-angiogenic treatments and for guiding their use in patients. ? ?

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL074443-02
Application #
6914968
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Buxton, Denis B
Project Start
2004-07-01
Project End
2005-12-31
Budget Start
2005-07-01
Budget End
2005-12-31
Support Year
2
Fiscal Year
2005
Total Cost
$381,250
Indirect Cost
Name
University of Virginia
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
Belcik, J Todd; Davidson, Brian P; Xie, Aris et al. (2017) Augmentation of Muscle Blood Flow by Ultrasound Cavitation Is Mediated by ATP and Purinergic Signaling. Circulation 135:1240-1252
Seol, Sang-Hoon; Davidson, Brian P; Belcik, J Todd et al. (2015) Real-time contrast ultrasound muscle perfusion imaging with intermediate-power imaging coupled with acoustically durable microbubbles. J Am Soc Echocardiogr 28:718-26.e2
Inaba, Yoichi; Davidson, Brian P; Kim, Sajeevani et al. (2014) Echocardiographic evaluation of the effects of stem cell therapy on perfusion and function in ischemic cardiomyopathy. J Am Soc Echocardiogr 27:192-9
Ryu, Jae Choon; Davidson, Brian P; Xie, Aris et al. (2013) Molecular imaging of the paracrine proangiogenic effects of progenitor cell therapy in limb ischemia. Circulation 127:710-9
Lindner, Jonathan R; Sinusas, Albert (2013) Molecular imaging in cardiovascular disease: Which methods, which diseases? J Nucl Cardiol 20:990-1001
Khanicheh, Elham; Qi, Yue; Xie, Aris et al. (2013) Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties. Arterioscler Thromb Vasc Biol 33:2187-92
Inaba, Yoichi; Lindner, Jonathan R (2012) Molecular imaging of disease with targeted contrast ultrasound imaging. Transl Res 159:140-8
Lindner, Jonathan R (2012) Molecular imaging of thrombus: technology in evolution. Circulation 125:3057-9
Khanicheh, Elham; Mitterhuber, Martina; Kinslechner, Katharina et al. (2012) Factors affecting the endothelial retention of targeted microbubbles: influence of microbubble shell design and cell surface projection of the endothelial target molecule. J Am Soc Echocardiogr 25:460-6
Davidson, Brian P; Kaufmann, Beat A; Belcik, J Todd et al. (2012) Detection of antecedent myocardial ischemia with multiselectin molecular imaging. J Am Coll Cardiol 60:1690-7

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