Identification of Genes Expressed in Atherosclerotic Plaque

Atherosclerosis

Serial Analysis of Gene Expression, Carotid Artery Plaque, Atherosclerosis

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.

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