It is unclear why individuals at risk for atherosclerosis develop more severe disease in some vascular beds than others, e.g. femoral arteries tend to develop much more severe disease than do brachial arteries. We hypothesize that these different susceptibilities are associated with regional differences in vascular endothelial function within those individuals. Wall shear stress is considered to be the primary hemodynamic stimulus for endothelial activity. Therefore, comparing the relationship between wall shear stress stimulus and endothelial response in different vascular beds may allow the evaluation of regional differences in endothelial function. Using phase-contrast magnetic resonance angiography, we have shown a linear relationship between wall shear stress during peak reactive hyperemia and resulting vessel dilatation in normal brachial arteries. We have also developed another method to assess endothelial stimulus response relationship by evaluating the time-course of endothelial regulation of wall shear stress following post-ischemic hyperemia, and a technique to assess circumferential distribution of wall shear stress in a single arterial cross-section.
The aims of this project are 1) to determine whether the endothelial stimulus-response relationships are altered in the presence of cardiovascular risk factors and in the presence of vascular disease, 2) to determine whether the relationships are sensitive to changes in endothelial function after a 6-week course of an HMG-Co A reductase inhibitor in subjects with hyperlipidemia, and 3) to determine whether the relationships or the circumferential stress distribution differ in different vascular beds. The investigators anticipate that this study will improve the ability to distinguish between normal and impaired endothelial function, and will enhance the understanding of atherosclerosis development. The proposal will involve mentorship, training, and resources from cardiovascular clinical research experts and several world-renown divisions of Johns Hopkins: Cardiovascular MRI, Biomedical Engineering, and The School of Public Health. The mentors, collaborators, environment, and research plan are ideal for achieving the applicant's long-term goal of becoming an independent clinical investigator, applying innovative engineering techniques toward patient-oriented cardiovascular problems.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL004477-05
Application #
6931899
Study Section
Special Emphasis Panel (ZHL1-CSR-F (O1))
Program Officer
Scott, Jane
Project Start
2001-08-13
Project End
2006-07-31
Budget Start
2005-08-01
Budget End
2006-07-31
Support Year
5
Fiscal Year
2005
Total Cost
$131,288
Indirect Cost
Name
Johns Hopkins University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218