Endothelial cell activation and/or injury is thought to be an initiating event in the development of atherosclerosis. This disease and its attendant complications such as coronary artery thrombosis represent the number one cause of mortality in this country. This renewal application of the Program Project, consisting of six individual scientific components and a core facility, sets specific objectives to define the mechanisms involved in the pathogenesis of thrombo-atherosclerosis. Through active collaborations, we will test the hypothesis that soluble mediators (eicosanoids, growth factors, cytokines) some of which are thromboregulators regulate vascular cell reactivity, cell adhesion, and phenotype.
Specific aims of this continuation application will focus on interactions between hematological and vascular cells in an attempt to elucidate the role of these interactions on the functional metabolic properties of the vessel wall. Particular emphasis will be placed on the role of fluid-phase and cell-associated thromboregulators (PGI/2, NO; ecto-ADPase) on vascular cell reactivity; cellular processes related to naturally-occurring """"""""negative"""""""" thromboregulators; the engagement of specific monocyte attachment receptors which transduce intracellular signals that alter the phenotype of vascular cells; and, coordinate induction of specific intracellular pathways which mediate arterial cell migration. The overall program project is designed to utilize the complimentary and non-overlapping research expertise of our vascular biology group to promote synergistic interactions. Our on-going collaborative efforts, where our PPG Vascular Biology group- (six principal investigators) has published 102 peer-reviewed, basic research papers together during the past 4 years, coupled with our major scientific discoveries, underscores the success of this program at Cornell. As a testament to our achievements, Cornell Medical School has recently developed a new Center of Vascular Biology headed by Dr. David Hajjar. These institutional funds (>$1.0 million) are ear-marked for modern capital improvements such as alterations/renovations and new equipment as well as faculty recruitment and development.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL046403-08
Application #
2750352
Study Section
Special Emphasis Panel (ZHL1-PPG-D (F1))
Project Start
1991-08-01
Project End
2001-07-31
Budget Start
1998-08-01
Budget End
1999-07-31
Support Year
8
Fiscal Year
1998
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Pathology
Type
Schools of Medicine
DUNS #
201373169
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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