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 82 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 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 the 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 nitric oxide 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 ad

Public Health Relevance

The process of arterial blood vessel growth (arteriogenesis) is little understood and there are no currently successful approaches to deal with its defects in clinical settings. 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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL107205-03
Application #
8607981
Study Section
Heart, Lung, and Blood Initial Review Group (HLBP)
Program Officer
Gao, Yunling
Project Start
2012-02-10
Project End
2017-01-31
Budget Start
2014-02-01
Budget End
2015-01-31
Support Year
3
Fiscal Year
2014
Total Cost
$1,710,619
Indirect Cost
$670,263
Name
Yale University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
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