Identification of Genes Expressed in Atherosclerotic Plaque
Identification of Genes Expressed in Atherosclerotic Plaque
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.