This study will measure and compare the levels of endothelial progenitor cells (EPCs) in the
blood of people with and without risk factors for atherosclerosis (hardening of the
arteries) to see if there is a relationship between these cells and cardiovascular risk
factors such as smoking, high cholesterol level and high blood pressure.
Healthy male volunteers between the ages of 21 and 55 years with and without heart disease
risk factors may be eligible for this study. Candidates must have no evidence of coronary
or peripheral vascular disease, proliferative retinopathy, or other chronic disease and no
history of cancer, migraine-type headache, cluster headache, raised intraocular pressure,
raised intracranial pressure, hyperthyroidism.
Participants will undergo the following procedures at the NIH Clinical Center:
- Medical history and physical examination
- Blood tests to measure EPC level and various risk and growth factors
- Brachial reactivity study - This ultrasound study tests how well the subject's arteries
widen. The subject rests on a bed for 30 minutes. An ultrasound measuring device is
placed over the artery just above the elbow. The size of the artery and blood flow
through it are measured before and after inflating a pressure cuff around the forearm.
The pressure cuff stops the flow of blood to the arm for a few minutes. After a
15-minute rest, the drug nitroglycerin is sprayed under the subject's tongue. Before
the nitroglycerin spray and 3 minutes after it, the size of the artery and blood flow
through it are measured again.
Evidence suggests that risk factors for atherosclerosis contribute to atherogenesis by
causing endothelial injury. However, little is known about determinants of endothelial cell
repair and regeneration. We propose that mobilization of endothelial progenitor cells
(EPCs) constitutes one mechanism for ongoing endothelial repair. EPCs are a bone marrow
derived cell population that can be isolated from peripheral blood. Among human peripheral
mononuclear cells, EPCs are relatively abundant with an estimated frequency of 1 in 500 to 1
in 1000 cells. Evidence suggests that EPCs can participate in angiogenesis under
pathophysiological circumstances. Under normal conditions, however, adult organisms
undergo little if any active angiogenesis. One explanation for this set of observations is
that high circulating levels of EPCs may exist to allow these cells to participate in
functions beyond angiogenesis. We hypothesize that one such function is in the repair of
ongoing endothelial injury. To test this hypothesis, we will measure peripheral blood EPC
activity by ascertaining the number of EPC colony forming units from peripheral blood
sampling. We intend to correlate this biological determinant with the degree of endothelial
dysfunction assessed by flow-mediated brachial artery reactivity, and an atherosclerotic
risk stratification method developed by the Framingham study. We hypothesize that a
correlation will exist between the atherosclerotic risk profile, endothelial function and
EPC activity and that the EPC activity will therefore become a novel surrogate biological
marker for cumulative cardiovascular risk.
Men: aged 21 and above with or without cardiovascular risk factors
Women - post menopausal (based on clinical history) with and without cardiovascular risk
History of cancer
Evidence of proliferative retinopathy
History of migraine-type headache
History of cluster headache
History of raised intraocular pressure
History of raised intracranial pressure
Hypersensitivity to organic nitrates
History of hyperthyroidism
Any intercurrent illness
Any other chronic disease not including cardiovascular risk factors.
No current medications including vitamins for at least 1 week.