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.
| Silber, Harry A; Lima, Joao A C; Bluemke, David A et al. (2007) Arterial reactivity in lower extremities is progressively reduced as cardiovascular risk factors increase: comparison with upper extremities using magnetic resonance imaging. J Am Coll Cardiol 49:939-45 |
| Silber, Harry A; Ouyang, Pamela; Bluemke, David A et al. (2005) Why is flow-mediated dilation dependent on arterial size? Assessment of the shear stimulus using phase-contrast magnetic resonance imaging. Am J Physiol Heart Circ Physiol 288:H822-8 |
| Silber, Harry A; Ouyang, Pamela; Bluemke, David A et al. (2005) A novel method for assessing arterial endothelial function using phase contrast magnetic resonance imaging: vasoconstriction during reduced shear. J Cardiovasc Magn Reson 7:615-21 |
