Endothelial cell activation/injury are initiating events in atherogenesis. This disease and its attendant complications such as thrombosis represent the major cause of mortality in this country. This renewal application, consisting of six scientific components and two core facilities, sets specific objectives to define the mechanisms involved in the pathogenesis of thrombo-atherosclerosis.. Through active collaboration, we will test the hypothesis that soluble mediators (e.g nitrogen oxides, reactive species, growth factors), and vascular cells to elucidate the signals governing functional and metabolic properties of the circulatory system. Particular emphasis will be placed on: the effects of fluid-phase and cell- associated thromboregulators (ectoADPase); NO; eicosanoids) on vascular and blood cell reactivity; modulation of cardiovascular stress responses by annexin II; the mechanisms by which the type B scavenger receptor, CD36; modulates vascular cell signaling; specific intracellular pathways mediating arterial cell migration and cytoskeleton reorganization; a molecular explanation of nitric oxide insufficiency in atherogenesis; and, studies on modulation of cycloooxygenase by nitrogen oxides and specific signalling cascades associated with vascular disease. The overall program is designed to utilize the complementary research expertise of our vascular biology group to promote synergistic interactions. We take pride that during the past 10 years, this has occurred.. Our on-going collaborative efforts, where our PPG Vascular Biology group has published 96 peer-reviewed original basic research papers during the past 4 years, coupled with our major scientific discoveries, underscores the success of this program. As a testament to our achievements, Cornell Medical School established a Center of Vascular Biology headed by Dr. David Hajjar. Institutional funds (>$1.0 million) are ear-marked for capital improvements, new equipment, and faulty development to help support this program.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046403-15
Application #
6943163
Study Section
Special Emphasis Panel (ZHL1-PPG-Q (F1))
Program Officer
Srinivas, Pothur R
Project Start
1991-08-01
Project End
2007-01-31
Budget Start
2005-08-23
Budget End
2007-01-31
Support Year
15
Fiscal Year
2005
Total Cost
$2,612,954
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Pathology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
Ramakrishnan, Devi Prasadh; Hajj-Ali, Rula A; Chen, Yiliang et al. (2016) Extracellular Vesicles Activate a CD36-Dependent Signaling Pathway to Inhibit Microvascular Endothelial Cell Migration and Tube Formation. Arterioscler Thromb Vasc Biol 36:534-44
Hajjar, Katherine A (2015) The Biology of Annexin A2: From Vascular Fibrinolysis to Innate Immunity. Trans Am Clin Climatol Assoc 126:144-55
Dassah, Maryann; Almeida, Dena; Hahn, Rebecca et al. (2014) Annexin A2 mediates secretion of collagen VI, pulmonary elasticity and apoptosis of bronchial epithelial cells. J Cell Sci 127:828-44
Anastasia, Agustin; Deinhardt, Katrin; Wang, Shiyang et al. (2014) Trkb signaling in pericytes is required for cardiac microvessel stabilization. PLoS One 9:e87406
Abbott, Geoffrey W; Tai, Kwok-Keung; Neverisky, Daniel L et al. (2014) KCNQ1, KCNE2, and Na+-coupled solute transporters form reciprocally regulating complexes that affect neuronal excitability. Sci Signal 7:ra22
Kennedy, David J; Chen, Yiliang; Huang, Wenxin et al. (2013) CD36 and Na/K-ATPase-?1 form a proinflammatory signaling loop in kidney. Hypertension 61:216-24
Zhou, Ming-Sheng; Chadipiralla, Kiranmai; Mendez, Armando J et al. (2013) Nicotine potentiates proatherogenic effects of oxLDL by stimulating and upregulating macrophage CD36 signaling. Am J Physiol Heart Circ Physiol 305:H563-74
Luo, Min; Hajjar, Katherine A (2013) Annexin A2 system in human biology: cell surface and beyond. Semin Thromb Hemost 39:338-46
Hajjar, David P; Gotto Jr, Antonio M (2013) Biological relevance of inflammation and oxidative stress in the pathogenesis of arterial diseases. Am J Pathol 182:1474-81
Siao, Chia-Jen; Lorentz, Christina U; Kermani, Pouneh et al. (2012) ProNGF, a cytokine induced after myocardial infarction in humans, targets pericytes to promote microvascular damage and activation. J Exp Med 209:2291-305

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