Thrombosis is a multifactorial process that directly contributes to nearly half of the mortality in the United States. It is now widely appreciated that insulin resistance and Type 2 Diabetes Mellitus (DM), often in the setting of obesity, are frequently identified as contributors to the development of arterial thrombotic phenomena, and comprise a major theme of this application. All of the Projects include Aims that systematically investigate the impact of diabetes and/or insulin resistance on thrombosis. This is motivated by the most recent data estimate that 18.2 million individuals in the United States have DM and a further 40 million may have impaired glucose tolerance or """"""""pre-diabetes"""""""". The component projects of this SCCOR address genetic, cellular and molecular mechanisms of thrombosis. In a mechanistic sense, this application targets three of the pre-eminent systems that contribute to the development of thrombosis, including platelet activation, thrombin biology and protease activated receptors (PARs), and the fibrinolytic system. This research program brings together investigators with diverse and complementary approaches to test hypotheses involving the mechanisms of thrombosis and how this process can be prevented. All of the Projects include Aims that directly involve human subjects. In fact, 12.5 of the 18 (69.4%) unique Specific Aims proposed in the five distinct Projects involve patient-oriented research. The combined skills of the investigators in fibrinolysis, the coupling of G-proteins to receptors, eicosanoid metabolism, platelet collagen receptors, and diabetes have been merged into a dynamic collaborative research group that will advance our understanding of the molecular mechanisms of arterial thrombosis in these high risk populations.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL081009-05
Application #
7808876
Study Section
Special Emphasis Panel (ZHL1-CSR-S (S1))
Program Officer
Link, Rebecca P
Project Start
2006-05-20
Project End
2012-02-29
Budget Start
2010-03-01
Budget End
2012-02-29
Support Year
5
Fiscal Year
2010
Total Cost
$3,392,221
Indirect Cost
Name
Vanderbilt University Medical Center
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Wong, L H; Elaine, Huang; Kong, R T (2016) Racial Differences Affecting Night Time Blood Pressure Dipping Groups in Hypertensive Patients. J Hypertens (Los Angel) 5:
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Hedrington, Maka S; Tate, Donna B; Younk, Lisa M et al. (2015) Effects of Antecedent GABA A Receptor Activation on Counterregulatory Responses to Exercise in Healthy Man. Diabetes 64:3253-61
Joy, Nino G; Tate, Donna B; Younk, Lisa M et al. (2015) Effects of Acute and Antecedent Hypoglycemia on Endothelial Function and Markers of Atherothrombotic Balance in Healthy Humans. Diabetes 64:2571-80
Perkins, Jennifer M; Joy, Nino G; Tate, Donna B et al. (2015) Acute effects of hyperinsulinemia and hyperglycemia on vascular inflammatory biomarkers and endothelial function in overweight and obese humans. Am J Physiol Endocrinol Metab 309:E168-76

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