Arteriogenesis is the process of formation of new arterial blood vessels during development or in the adult circulation. In development it entails formation of new endothelial vascular structures with arterial identity as defined by expression of key markers such ephrin B2 and neuropilin 1 followed by acquisition of the media and adventitia. In the adult circulation new arteries arise either by expansion of the pre-existing arterial vascular structures or de novo. Deletion of VEGF, its receptor VEGFR2 or key intracellular signaling mediators results in failure of arterial vasculature development. Defective arteriogenesis is noted in other setting including deletion of eNOS or in disease states such as diabetes and hypercholesterolemia and this failure contributes greatly to morbidity u and mortality associated with these diseases. Nevertheless, the entire process is little understood and there are no currently successful approaches to deal with its defects in clinical settings. Understanding of molecular mechanism regulating arteriogenesis would be of great benefit to our understanding of pathobiology of major cardiovascular illnesses and to development of new therapeutic approaches to combat them. In this PPG we propose a comprehensive approach to investigate the molecular basis of arteriogenesis and to develop new intellectual framework for therapeutic advances in this field. To this end, we will investigate a novel signaling pathway that seems to be critical to arteriogenesis (Project 1), study contributions of nitricoxide and the extracellular matrix (Project 2), evaluate the central role of mTOR in balancing various arteriogenic signaling inputs (Project 3) and determine the role of shear stress and other mechanical factors in initiating arteriogenesis in adult tissues (Project 4). The purpose of Core A is to coordinate programs of the entire PPG by providing scientific administration, scientific enhancement (speakers and seminars), and providing grant and program management.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
1P01HL107205-01A1
Application #
8250619
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Project Start
Project End
Budget Start
2012-02-10
Budget End
2013-01-31
Support Year
1
Fiscal Year
2012
Total Cost
$79,801
Indirect Cost
$31,643
Name
Yale University
Department
Type
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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