Identification of Genes Expressed in Atherosclerotic Plaque
Condition: Atherosclerosis
MeSH terms: Atherosclerosis; Plaque, Atherosclerotic
Study type: Observational

Summary: 
      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
    

Detailed description: 
      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.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Patients
      
Keywords: Serial Analysis of Gene Expression; Carotid Artery Plaque; Atherosclerosis