Abstract

This is a resubmission seeking renewal of a 20-year program encompassing 5 sub-projects which investigate mechanisms and implications of various responses to hypoxia. Three of these continue a long standing line of investigation concerning the pulmonary circulation-the development of vasoconstriction and pulmonary hypertension in response to hypoxia. The proposed studies explore direct effects of hypoxia on pulmonary vascular endothelium and smooth muscle, genetic determinants, and the role of the adventitial fibroblasts in the development of hypoxic pulmonary hypertension. Other projects propose to investigate the ventilatory response to hypoxia and its modulation by genetic factors and the effect of hypoxia on systemic vascular response to pregnancy. There is considerable cross-talk amongst these projects with respect to common underlying scientific principles, shared expertise and resources. Information resulting from these studies should provide insights into the effects of hypoxia on the pulmonary circulation, ventilatory control, and systemic circulatory changes in pregnancy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Program Projects (P01)
Project #
5P01HL014985-25
Application #
2392570
Study Section
Special Emphasis Panel (ZHL1-PPG-F (F1))
Project Start
1977-04-01
Project End
1998-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
25
Fiscal Year
1997
Total Cost
Indirect Cost

  Institution

Name
University of Colorado Denver
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
065391526
City
Aurora
State
CO
Country
United States
Zip Code
80045

  Publications

Graham, Brian B; Kumar, Rahul; Mickael, Claudia et al. (2018) Vascular Adaptation of the Right Ventricle in Experimental Pulmonary Hypertension. Am J Respir Cell Mol Biol 59:479-489
Wick, Marilee J; Harral, Julie W; Loomis, Zoe L et al. (2018) An Optimized Evans Blue Protocol to Assess Vascular Leak in the Mouse. J Vis Exp :
Reisz, Julie A; Barrett, Alexander S; Nemkov, Travis et al. (2018) When nature's robots go rogue: exploring protein homeostasis dysfunction and the implications for understanding human aging disease pathologies. Expert Rev Proteomics 15:293-309
Friesen, Richard M; Schäfer, Michal; Ivy, D Dunbar et al. (2018) Proximal pulmonary vascular stiffness as a prognostic factor in children with pulmonary arterial hypertension. Eur Heart J Cardiovasc Imaging :
Stenmark, Kurt R; Tuder, Rubin M (2018) Peroxisome Proliferator-activated Receptor ? and Mitochondria: Drivers or Passengers on the Road to Pulmonary Hypertension? Am J Respir Cell Mol Biol 58:555-557
Jiang, Xinguo; Tian, Wen; Tu, Allen B et al. (2018) Endothelial HIF-2? is Required for the Maintenance of Airway Microvasculature. Circulation :
Das, Mita; Zawada, W Michael; West, James et al. (2018) JNK2 regulates vascular remodeling in pulmonary hypertension. Pulm Circ 8:2045894018778156
Tamosiuniene, Rasa; Manouvakhova, Olga; Mesange, Paul et al. (2018) Dominant Role for Regulatory T Cells in Protecting Females Against Pulmonary Hypertension. Circ Res 122:1689-1702
Blum, Lisa K; Cao, Richard R L; Sweatt, Andrew J et al. (2018) Circulating plasmablasts are elevated and produce pathogenic anti-endothelial cell autoantibodies in idiopathic pulmonary arterial hypertension. Eur J Immunol 48:874-884
Kumar, Rahul; Graham, Brian (2018) IL-33-HIF1? Axis in Hypoxic Pulmonary Hypertension. EBioMedicine 33:8-9

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