; The surgical/imaging cores (Core B) will provide the expertise and quality control for surgical models in evaluation of the signaling pathways associated with arteriogenesis, preparation of animals for imaging,performing multi-modality imaging, and coordinating image analyses for all projects. Recently renovated Yale facilities are uniquely capable of conducting advanced imaging studies on acute and chronically instrumented animals. The small animal surgical/imaging core includes capacity for anesthesia, hemodynamic monitoring, microsurgery, dedicated animal housing, facilities for preparation of ex vivo specimen and contrast, and an imaging suite that includes high-resolution (25-100 um) in vivo microCT scanners, and ultra-high resolution (8 um) specimen microCT, deep muscle laser Doppler imaging system, and scanning laser Doppler imager. The surgical core will provide two well established murine models of hindlimb ischemia, and a vasoreactivity model. Previous studies have suggested the importance of standardized surgical interventions with minimal trauma to the animals. To assure uniformity of the experimental models between projects an experienced surgical team will perform all of the surgical interventions and peri-operative care. The imaging core will serve as a central resource for;preparation of specimens and contrast agents, animal preparation and monitoring for in vivo imaging, image acquisition and reconstruction, image archive, and will assist with the supervision of registration of the image data derived from multiple imaging systems and image quantification. The imaging core will include individuals with unique technical qualifications and sufficient dedicated time to assure consistent high quality images. Registration and analysis of images from multiple imaging systems will be provided by individuals with computer and bioengineering expertise supervised by faculty from Departments of Medicine, Diagnostic Radiology, and Biomedical Engineering with recognized expertise in the imaging sciences. This surgical/imaging team will be supervised by Dr. Sinusas, who will serve as the director of Core B. This team will advise participating investigators regarding the appropriate application of animal models and imaging.

Public Health Relevance

The discovery of a signaling cascade controlling growth of new arteries will provide new insights and tools into developing new therapeutic strategies for treatment of atherosclerotic cardiovascular diseases including coronary, cerebral and peripheral vascular diseases.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Program Projects (P01)
Project #
Application #
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Yale University
New Haven
United States
Zip Code
Calabro, Nicole E; Kristofik, Nina J; Kyriakides, Themis R (2014) Thrombospondin-2 and extracellular matrix assembly. Biochim Biophys Acta 1840:2396-402
Ricard, Nicolas; Simons, Michael (2014) Fox(y) regulators of VEGF receptors. Circ Res 115:683-5
Faber, James E; Chilian, William M; Deindl, Elisabeth et al. (2014) A brief etymology of the collateral circulation. Arterioscler Thromb Vasc Biol 34:1854-9
Sundaram, Sumati; Echter, Andreana; Sivarapatna, Amogh et al. (2014) Small-diameter vascular graft engineered using human embryonic stem cell-derived mesenchymal cells. Tissue Eng Part A 20:740-50
Ju, Rong; Zhuang, Zhen W; Zhang, Jiasheng et al. (2014) Angiopoietin-2 secretion by endothelial cell exosomes: regulation by the phosphatidylinositol 3-kinase (PI3K)/Akt/endothelial nitric oxide synthase (eNOS) and syndecan-4/syntenin pathways. J Biol Chem 289:510-9
Zhang, Xi; Simons, Michael (2014) Receptor tyrosine kinases endocytosis in endothelium: biology and signaling. Arterioscler Thromb Vasc Biol 34:1831-7
Huang, Angela H; Niklason, Laura E (2014) Engineering of arteries in vitro. Cell Mol Life Sci 71:2103-18
Goodwin, Julie E; Feng, Yan; Velazquez, Heino et al. (2014) Loss of the endothelial glucocorticoid receptor prevents the therapeutic protection afforded by dexamethasone after LPS. PLoS One 9:e108126
Morris, Aaron H; Kyriakides, Themis R (2014) Matricellular proteins and biomaterials. Matrix Biol 37:183-91
Gui, Liqiong; Boyle, Michael J; Kamin, Yishai M et al. (2014) Construction of tissue-engineered small-diameter vascular grafts in fibrin scaffolds in 30 days. Tissue Eng Part A 20:1499-507

Showing the most recent 10 out of 16 publications