Diabetes in the United States today is an explosive major public health issue that directly impacts cardiovascular morbidity and mortality. One major reason for these devastating cardiovascular complications is that diabetics exhibit impaired collateral vessel development. Formation of functional collateral blood vessels is the primary adaptive mechanism in humans to blood flow obstruction. In this project we will explore the role of advanced glycation end products and the specific receptor for advanced glycation end products (RAGE) in inhibition of collateral blood vessel formation. We have developed exciting preliminary data showing that advanced glycation end products dramatically inhibit collateral vessel formation. Moreover, we have presented preliminary data that demonstrate a central role for RAGE signaling in monocytes in this process. The proposed studies will first examine the overall role of RAGE in inhibiting collateral vessel formation. Subsequent aims will study the specific contributions of RAGE in monocytes and T cells as these two inflammatory cells types have been shown by us and others to be critical for the formation of collateral blood vessels. Additional studies will examine the role of reactive oxygen species as crucial signaling intermediates in RAGE signal transduction in both monocytes and T cells. Through these studies, we will develop a comprehensive and critical assessment of the role of RAGE signaling in inflammatory cells and the subsequent impact on collateral vessel formation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL095070-04
Application #
8380232
Study Section
Special Emphasis Panel (ZHL1-PPG-A)
Project Start
Project End
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$383,513
Indirect Cost
$117,274
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yeligar, Samantha M; Kang, Bum-Yong; Bijli, Kaiser M et al. (2017) PPAR? Regulates Mitochondrial Structure and Function and HPASMC Proliferation. Am J Respir Cell Mol Biol :
Caroti, Courtney M; Ahn, Hyunhee; Salazar, Hector F et al. (2017) A Novel Technique for Accelerated Culture of Murine Mesenchymal Stem Cells that Allows for Sustained Multipotency. Sci Rep 7:13334
Kim, Chan Woo; Pokutta-Paskaleva, Anastassia; Kumar, Sandeep et al. (2017) Disturbed Flow Promotes Arterial Stiffening Through Thrombospondin-1. Circulation 136:1217-1232
Kumar, Sandeep; Kang, Dong-Won; Rezvan, Amir et al. (2017) Accelerated atherosclerosis development in C57Bl6 mice by overexpressing AAV-mediated PCSK9 and partial carotid ligation. Lab Invest 97:935-945
Feng, Shuang; Bowden, Neil; Fragiadaki, Maria et al. (2017) Mechanical Activation of Hypoxia-Inducible Factor 1? Drives Endothelial Dysfunction at Atheroprone Sites. Arterioscler Thromb Vasc Biol 37:2087-2101
Xu, Qian; Huff, Lauren P; Fujii, Masakazu et al. (2017) Redox regulation of the actin cytoskeleton and its role in the vascular system. Free Radic Biol Med 109:84-107
Hammadah, Muhammad; Al Mheid, Ibhar; Wilmot, Kobina et al. (2017) Telomere Shortening, Regenerative Capacity, and Cardiovascular Outcomes. Circ Res 120:1130-1138
Hu, Shuhong; Liu, Yifei; You, Tao et al. (2017) Vascular Semaphorin 7A Upregulation by Disturbed Flow Promotes Atherosclerosis Through Endothelial ?1 Integrin. Arterioscler Thromb Vasc Biol :
Heath, Jack M; Fernandez Esmerats, Joan; Khambouneheuang, Lucky et al. (2017) Mechanosensitive microRNA-181b Regulates Aortic Valve Endothelial Matrix Degradation by Targeting TIMP3. Cardiovasc Eng Technol :
Hernandes, Marina S; Lass├Ęgue, Bernard; Griendling, Kathy K (2017) Polymerase ?-interacting Protein 2: A Multifunctional Protein. J Cardiovasc Pharmacol 69:335-342

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