Research
Despite remarkable recent progress in molecular and vascular biology research, little has been achieved in adapting traditional imaging modalities to detect molecular pathobiology in vivo. Molecular imaging provides a unique opportunity to link vascular and molecular biology with imaging, ultimately leading to the development of novel imaging approaches both for research and clinical diagnostics.
Our research effort comprises of three inter-connected dimensions: a) Through basic vascular biology research we identify relevant molecular processes and potential targets for imaging (and therapeutics); b) We use the state-of-the-art technology to develop novel tracers targeted at relevant molecular markers, establishing innovative molecular vascular imaging protocols in animal models of human disease; c) We exploit these techniques to further advance vascular biology and clinical research. We have made significant progress towards achieving these goals in the past few years.
Vascular Biology
Our federally funded studies of the pathophysiology of vascular remodeling have led to the identification novel molecular markers, including a neuropilin-like protein, ESDN, as a potential target for diagnosis and therapy of vascular remodeling.
We have demonstrated that ESDN is upregulated in vascular remodeling, and have defined its function as regulator of vascular cell proliferation in vivo. We are currently in the process of defining other aspects of ESDN function, including its role in growth factor and integrin signaling pathways, and identification of ESDN ligands.
Related Citations
Li X, Jung JJ, Nie L, Razavian M, Zhang J, Samuel VT, Sadeghi MM: A neuropilin-like protein, ESDN regulates insulin signaling and sensitivity. Am J Physiol Heart Circ Physiol. 2016 Feb 26; 2016 Feb 26. PMID: 26921437
Nie L, Guo X, Esmailzadeh L, Zhang J, Asadi A, Collinge M, Li X, Kim JD, Woolls M, Jin SW, Dubrac A, Eichmann A, Simons M, Bender JR, Sadeghi MM: Transmembrane protein ESDN promotes endothelial VEGF signaling and regulates angiogenesis. J Clin Invest. 2013 Dec; 2013 Nov 1. PMID: 24177422
Zhang J, Silva T, Yarovinsky T, Manes TD, Tavakoli S, Nie L, Tellides G, Pober JS, Bender JR, Sadeghi MM: VEGF blockade inhibits lymphocyte recruitment and ameliorates immune-mediated vascular remodeling. Circ Res. 2010 Aug 6; 2010 Jun 10. PMID: 20538685
Guo X, Nie L, Esmailzadeh L, Zhang J, Bender JR, Sadeghi MM: Endothelial and smooth muscle-derived neuropilin-like protein regulates platelet-derived growth factor signaling in human vascular smooth muscle cells by modulating receptor ubiquitination. J Biol Chem. 2009 Oct 23; 2009 Aug 19. PMID: 19696027
Preclinical Molecular Imaging
We have identified and validated avß3 integrin activation as a target for imaging the proliferative process in vascular remodeling, and have demonstrated the suitability of αvß3 integrin and VEGF-receptor targeting for imaging graft arteriosclerosis and vascular remodeling. Matrix metalloproteinase (MMP) activation, as a key regulator of vascular remodeling, was targeted for in vivo imaging of injury-induced vascular remodeling and aneurysm formation using high resolution microSPECT imaging in conjunction with CT angiography for anatomical localization. In parallel, we work on development of novel probes that selectively and specifically target the molecules that are involved in vascular remodeling and inflammation. We further validate the newly developed fluorescence- and radionuclide-labeled probes using in vitro, ex vivo, and in vivo techniques.
Related Citations
Zhang J, Razavian M, Tavakoli S, Nie L, Tellides G, Backer JM, Backer MV, Bender JR, Sadeghi MM: Molecular imaging of vascular endothelial growth factor receptors in graft arteriosclerosis. Arterioscler Thromb Vasc Biol. 2012 Aug; 2012 Jun 21. PMID: 22723442
Razavian M, Marfatia R, Mongue-Din H, Tavakoli S, Sinusas AJ, Zhang J, Nie L, Sadeghi MM: Integrin-targeted imaging of inflammation in vascular remodeling. Arterioscler Thromb Vasc Biol. 2011 Dec; 2011 Sep 22. PMID: 21940943
Razavian M, Zhang J, Nie L, Tavakoli S, Razavian N, Dobrucki LW, Sinusas AJ, Edwards DS, Azure M, Sadeghi MM: Molecular imaging of matrix metalloproteinase activation to predict murine aneurysm expansion in vivo. J Nucl Med. 2010 Jul; 2010 Jun 16. PMID: 20554725
Golestani R, Razavian M, Nie L, Zhang J, Jung JJ, Ye Y, de Roo M, Hilgerink K, Liu C, Robinson SP, Sadeghi MM: Imaging vessel wall biology to predict outcome in abdominal aortic aneurysm. Circ Cardiovasc Imaging. 2015 Jan; 2014 Dec 30. PMID: 25550400
MMP
MMP-targeted microSPECT/CT imaging of CaCl2-induced carotid artery aneurysm