Vascular inflammation and oxidative stress are fast becoming key components of aging science. However, the interaction been these two entities is often not addressed in current research. To address these issues, a basic understanding of the pathophysiology of oxidative stress and vascular inflammation that results in vaso-occlusion is required. Closing this gap in knowledge will be the focus of this proposal. We will examine the link between hemolysis, oxidative stress, vascular inflammation and vaso-occlusion during aging using sickle cell disease as a model. We will learn from nature's protective response to excessive heme burden, the induction of HO-1. We will modulate HO-1 to decrease oxidative stress and vascular inflammation and prevent vaso-occlusion. New therapies which can decrease oxidative stress and vascular inflammation will result from these studies. Preventing vaso-occlusion will protect organ function, improve quality of life, and reduce morbidity and mortality. This proposal supports the mission of NIA by its focus on research that will develop and evaluate innovative treatments related to the prevention and treatment of oxidative stress and vascular inflammation. This proposal will advance the field by providing a clear understanding of the link between hemolysis, vascular inflammation, oxidative stress, and vaso-occlusion. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30AG030909-01
Application #
7328912
Study Section
Special Emphasis Panel (ZRG1-F10-H (21))
Program Officer
Finkelstein, David B
Project Start
2007-07-01
Project End
2011-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
1
Fiscal Year
2007
Total Cost
$32,964
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Beckman, Joan D; Chen, Chunseng; Nguyen, Julia et al. (2011) Regulation of heme oxygenase-1 protein expression by miR-377 in combination with miR-217. J Biol Chem 286:3194-202
Beckman, Joan D; Belcher, John D; Vineyard, Julie V et al. (2009) Inhaled carbon monoxide reduces leukocytosis in a murine model of sickle cell disease. Am J Physiol Heart Circ Physiol 297:H1243-53