Vascular complications in elderly people with diabetes continue to be major health problems throughout the world, yet lipid-associated mechanism for disrupting vascular integrity is unclear. As a major type of covalent lipid modifications, reversible protein S-palmitoylation has emerged as a potentially critical post-translational process in signaling pathway. Our studies suggest that the protein depalmitoylation enzyme APT1 is critical for ischemic vascular remodeling that is relevant to peripheral artery disease. By integrating in vitro studies, mouse models and patient specimen analysis, the research plan will lead to the identification and characterization of APT1-dependent R-Ras palmitoylation dynamics in vascular complications of diabetic patients. The result of the study will warrant the future focus on the role of lipid modification in pathophysiology and offer the promise of discovering novel targets for peripheral artery disease in elderly patient with diabetes.

Public Health Relevance

Lipids can alter protein function by a direct modification. Our objective is to study dynamic lipid modification in the essential pathways in blood vessels and help us to design novel treatment strategies for cardiovascular complications of elderly people with diabetes.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AG051900-02
Application #
9346669
Study Section
Vascular Cell and Molecular Biology Study Section (VCMB)
Program Officer
Williams, John
Project Start
2016-09-15
Project End
2018-05-31
Budget Start
2017-06-15
Budget End
2018-05-31
Support Year
2
Fiscal Year
2017
Total Cost
$190,625
Indirect Cost
$65,625
Name
Washington University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130