Identification of Genes Expressed in Atherosclerotic Plaque

Status:	Completed
Conditions:	Peripheral Vascular Disease, Cardiology
Therapuetic Areas:	Cardiology / Vascular Diseases
Healthy:	No
Age Range:	21 - 100
Updated:	9/20/2018
Start Date:	August 9, 2002

Identification of Genes Expressed in Atherosclerotic Plaques

This study will identify genes and proteins in the blood of patients with atherosclerosis and
in that of normal volunteers. The findings will be compared to determine the influence of
these substances on the development of atherosclerosis a narrowing and hardening of blood
vessel walls by deposits of fatty substances. Blood vessel blockage caused by atherosclerosis
can impede blood flow and cause stroke, heart attack and poor limb circulation. The
information from this study may lead to better ways to detect, prevent and treat these
diseases.

Healthy volunteers and patients scheduled for carotid endarterectomy at Suburban Hospital in
Bethesda, Maryland, are eligible for this study. Carotid endarterectomy is a surgical
procedure in which the inner layer of the carotid artery (neck artery supplying blood to the
brain) is scraped away to open the blocked vessel. Participants will undergo the following
tests and procedures:

Patients

- Blood sample: Collection of about 32 cc (8 tablespoons) of blood for genetic and protein
analysis

- Tissue sample: Collection of a piece of diseased blood vessel discarded from the
endarterectomy procedure

- Review of records: Review of medical records for information about past illnesses,
medications, tests, and so forth, if needed

Normal Volunteers

- Blood samples: Collection of about 32 cc (8 tablespoons) of blood for genetic and
protein analysis

- Carotid artery ultrasound: Ultrasound imaging of the neck arteries for detection of any
blockage

- Electrocardiogram: Recording of the electrical activity of the heart to detect any
abnormalities in heart rhythm

- Echocardiogram: Ultrasound examination to detect possible abnormalities of the heart
muscle

- Cardiac stress test: Treadmill stress test to detect possible heart vessel blockage (for
subjects who have not had a cardiac stress test in the past year)

- Review of records: Review of medical records for information about past illnesses,
medications, tests, and so forth, if needed

Significant progress has been made in the prevention and treatment of atherosclerosis, but it
continues to be a leading cause of morbidity and mortality in our society. The problem will
become even more significant as an increasing proportion of the population ages. The goal of
the proposed project is to advance our understanding of the genetic mechanisms of
atherosclerosis. We propose to identify genes selectively expressed in peripheral monocytes
of patients with atherosclerosis and in macrophages and endothelial cells of atherosclerotic
plaques. We will examine gene expression profiles in purified subpopulations of cells using
Serial Analysis of Gene Expression (SAGE) that requires only minute amounts of RNA, enabling
the study of small homogeneous populations of cells. This sequence-based high-throughput gene
expression profiling technique has the advantage of not requiring prior knowledge of the
expressed gene sequences, allowing the discovery of new genes. With the completion of the
human genome sequence, the SAGE technique is an ideal tool for comprehensively characterizing
the transcriptomes of the important cells involved in atherosclerosis. This proposal is an
exploratory study to find candidates, both known and unknown genes, which will be used for
more extensive and statistically powered projects in the future. The insights obtained will
be used for elucidating the pathogenesis of atherosclerosis and for developing new simple,
sensitive and specific tests for early disease diagnosis. In addition, the new insights
obtained may lead to the development of novel therapeutic strategies for disease prevention
and treatment.

- INCLUSION CRITERIA:

Any adult patient with carotid artery disease or known atherosclerosis capable of giving
informed consent.

INCLUSION CRITERIA FOR MEDICATION TREATED SUBJECT:

Any adult with normal total cholesterol (less than 200 mg/dl) and blood pressure (systolic
less than 140 and diastolic less than 90).

INCLUSION CRITERIA FOR NORMAL BRONCHOSCOPY SUBJECT:

Any healthy adult subject with no history of peripheral or coronary artery disease, who is
eligible for bronchoalveolar lavage per Protocol 99-H-0068 and capable of giving informed
consent.

EXCLUSION CRITERIA:

Unable to give consent

History of chronic infections, vasculitis or any other inflammatory disease

History of neoplastic disease or chemotherapy treatment

Immunosuppressive medications other than common over-the-counter drugs such as aspirin or
acetaminophen

EXCLUSION CRITERIA FOR MEDICATION TREATED SUBJECT:

Subject with abnormal liver and renal function tests on pretreatment screening or currently
taking a statin or ACE inhibitor medication.

EXCLUSION CRITERIA FOR NORMAL BRONCHOSCOPY SUBJECT:

Any exclusion criteria for normal subject listed in Protocol 99-H-0068.

We found this trial at

sites

Suburban Hospital

8600 Old Georgetown Road
Bethesda, Maryland 20814

301-896-3100