The purpose of this project is to improve our understanding of arteriogenesis in ischemia. This process, consisting of outward remodeling of pre-existing arteriole anastomoses and formation of new or """"""""neo-collaterals"""""""", is not well understood. Moreover, many patients with ischemic disease show a deficit in collateral development. A mouse strain with a severe deficiency in recovery of perfusion after artery ligation has been identified, but the reasons for the impairment are unknown.
Aim I will use new methods we have developed for imaging arteriogenesis, will introduce a new strategy for study of neo-collateral formation, and will test the hypothesis that formation of neo-collaterals is defective in the strain. There is evidence that the morphogenic pathway, Sonic hedgehog-notch, which mediates early vascular development, may be reactivated in adults during injury and/or remodeling. A role for this pathway in arteriogenesis has not been studied. Our preliminary data suggest Shh signaling is important in collateral maturation. Therefore, Aim II will examine the hypothesis that Shh-notch signaling contributes to pre-existing collateral maturation and neo-collateral formation, and that it is defective in the impaired strain.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32HL080847-02
Application #
7038253
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Meadows, Tawanna
Project Start
2005-03-18
Project End
2008-03-17
Budget Start
2006-03-18
Budget End
2007-03-17
Support Year
2
Fiscal Year
2006
Total Cost
$50,428
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Physiology
Type
Schools of Medicine
DUNS #
608195277
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
Chalothorn, Dan; Faber, James E (2010) Strain-dependent variation in collateral circulatory function in mouse hindlimb. Physiol Genomics 42:469-79
Chalothorn, Dan; Zhang, Hua; Smith, Jennifer E et al. (2009) Chloride intracellular channel-4 is a determinant of native collateral formation in skeletal muscle and brain. Circ Res 105:89-98
Clayton, Jason A; Chalothorn, Dan; Faber, James E (2008) Vascular endothelial growth factor-A specifies formation of native collaterals and regulates collateral growth in ischemia. Circ Res 103:1027-36
Lewis, Chandani; Zhu, Weifei; Pavkov, Mircea L et al. (2008) Arginase blockade lessens endothelial dysfunction after thrombosis. J Vasc Surg 48:441-6
Chalothorn, Dan; Clayton, Jason A; Zhang, Hua et al. (2007) Collateral density, remodeling, and VEGF-A expression differ widely between mouse strains. Physiol Genomics 30:179-91