USDOE Human Subjects Research Database, fiscal year 1995

Lawrence Berkeley National Laboratory

Project Identifier: LBNL-93-097-H01

Project Title:

Extracellular HDL-Assembly with Apolipoprotein-AI Variants (see LBL-93-2-79 in 1994 database)

Principle Investigator: Dr. John Bielicki

Project started in: 1993

Fiscal Year 1995 Funding for Research on Human Subjects:

Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.

Funding Sources:

Non-Federal: American Heart Association Post Doctoral Fellowship

Amount: $2,000 (Est.)

Information on Use of Human Subjects:

Project involves use of multiple protocols/subprojects.
Number of protocols/subprojects associated with this project: 1

Protocol/Subproject # 1
Protocol/Subproject Identifier: 95-2-128

IRB Review:
Type of Review: Full Board
Most Recent Approval: February 17, 1995
IRB Approval Number: 95-2-128

Number of Human Subjects in the Last Reporting Period for this Project: 1
(Reporting periods vary.)

Type of Human Subjects Involvement:

Collection of Bodily Materials:

Collection of personally identifiable bodily materials (blood or blood products, cells, tissue, organs, waste).

• Use of cells cultured in a laboratory.
• Use of bodily materials collected from subjects specifically for this project.
• Use of existing bodily materials that were collected for another purpose or project.

Questionnaires, Surveys, Epidemiological Studies:

Use of personally identifiable data from questionnaires, surveys, or epidemiological studies.

• Use of data collected from subjects specifically for this project.
• Use of existing data that were collected for another purpose or project.

(a. Objectives, b. Methodology, c. Ionizing Radiation, Radioactive Substances, or Chemical Substances to which human subjects are exposed, d. Involvement of Human Subjects [d.1. procedures used, d.2. risks if any])

OBJECTIVES

To test the hypothesis that mutant forms of Apolipoprotein-AI (apo AI) are less effective in constructing the high density lipoproteins which protect against atherosclerosis. All experimental work is with cells in culture. Human serum collected under another protocol (LBNL-79-106-H02, "Metabolic & Genetic Origins of Lipoprotein Subclasses") is used as the source of lecithin:cholesterol acyltransferase (LCAT). The purified LCAT is used to determine if the high density lipoproteins (HDL) formed by mutant cells in culture are acted upon the same as HDL from normal cells. Societal benefits may include the provision of additional evidence that the release of lipid from cells to free-apolipoproteins is a physiologically significant process in that mutations within apo AI which interfere with HDL assembly have clinical presentations.

METHODOLOGY

Human serum collected under another protocol is used as the source of lecithin:cholesterol acyltransferase, an enzyme used to test for high density lipoprotein activation. The extracellular assembly of HDL particles will be assessed, and the structure and function of the different particles compared. These characterizations will proceed in series: 1) quantification of the extent of apolipoprotein lipidation, 2) determinations of the sizes and chemical compositions of nascent-HDL particles, 3) examination of the efficiency of mutant apo AI to promote cholesterol efflux from cells, and 4) investigations of the ability of mutant-HDL to activate LCAT.

IONIZING RADIATION, RADIOACTIVE SUBSTANCES, OR CHEMICAL SUBSTANCES

None.

INVOLVEMENT OF AND RISKS TO HUMAN SUBJECTS

This study does not present any additional risks to human subjects. (It uses blood collected under another protocol.)