Identification of Genes Expressed in Atherosclerotic Plaque

Sponsor

National Heart, Lung, and Blood Institute (NHLBI) (NIH)

Overall Status

Completed

CT.gov ID

NCT00353730

Collaborator

(none)

Enrollment

Locations

98.7

Actual Duration (Months)

34.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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

Condition or Disease	Intervention/Treatment	Phase
Atherosclerosis

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.

Study Design

Study Type:

Observational

Actual Enrollment :

69 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Identification of Genes Expressed in Atherosclerotic Plaques

Actual Study Start Date :

Oct 21, 2002

Actual Primary Completion Date :

Mar 16, 2005

Actual Study Completion Date :

Jan 12, 2011

Outcome Measures

Primary Outcome Measures

To identify known and unknown genes involved in the pathogenesis of atherosclerosis for further analyses. [ongoing]
To identify known and unknown genes involved in the pathogenesis of atherosclerosis.

Secondary Outcome Measures

To identify atherosclerosis-specific genes expressed in peripheral monocytes, plaque macrophages or endothelial cells that may serve as early markers for disease diagnosis [ongoing]
To identify atherosclerosis-specific genes expressed in peripheral monocytes, plaque macrophages or endothelial cells that may serve as early markers for disease diagnosis
To identify genes expressed early in the pathogenesis of atherosclerosis that may be targeted for disease prevention. [ongoing]
To identify genes expressed early in the pathogenesis of atherosclerosis that may be targeted for disease prevention.

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Suburban Hospital	Bethesda	Maryland	United States	20814
2	National Institutes of Health Clinical Center, 9000 Rockville Pike	Bethesda	Maryland	United States	20892