LP-A PHENOTYPE ATHEROSCLEROSIS

  • Rainwater, David L (PI)

    Project: Research project

    Project Details

    Description

    High levels of Lp(a) (lipoprotein (a)) are related to greater risk of
    atherosclerosis in humans, although precise details of the
    relationship are not known. The baboon, a primate model for
    research on the interaction of lipoproteins and atherosclerosis,
    possesses Lp (a) that is similar to human Lp (a) in every respect.
    We have developed techniques for quantitating aspects of Lp(a)
    phenotype, including total serum concentration, individual isoform
    levels, and the lipoprotein density. The goals for this proposal are
    to determine the relationship between Lp(a) phenotype and
    atherosclerosis in the baboon model, and to develop a better
    understanding of the genetic and dietary factors that mediate
    Lp(a) phenotype. These studies are important to the long-term
    objective of developing therapies in the baboon model that will
    help reduce the risk of cardiovascular disease due to the presence
    of Lp(a). This proposal has five Specific Aims: 1) determine the
    frequency of occurrence of Lp(a) phenotypes in a population of
    unrelated baboons; 2) test the hypothesis that Lp(a) phenotype is
    related to extent of arterial atherosclerotic lesions. Lp(a)
    phenotype in 320 baboons will be evaluated in relation to extent
    of atherosclerosis assessed following necropsy; 3) test the
    hypothesis that postprandial forms of Lp(a) are related to extent
    of atherosclerotic lesions. We will determine the postprandial
    Lp(a) phenotype (120 baboons) which will be evaluated in relation
    to extent of atherosclerosis; 4) test the hypothesis that Lp(a)
    phenotype is responsive to diet. Lp(a) phenotype will be
    determined and correlated with a consistent change in levels of
    dietary fat and cholesterol in 100 baboons. Ethanol is reported to
    decrease human Lp(a) levels, and we will correlate Lp(a)
    phenotype with changes in amount of dietary ethanol in eight
    baboons; and 5) test the hypothesis that two major genes control
    the various aspects of Lp(a) phenotype using samples from
    members of a pedigreed colony. Understanding dietary and
    genetic influences on Lp(a) phenotype, and its association with
    atherosclerosis, will help us plan strategies to reduce the risk of
    cardiovasular disease due to the presence of Lp(a).
    StatusFinished
    Effective start/end date4/1/886/30/94

    Funding

    • National Institutes of Health: $10,936.00
    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health: $141,084.00
    • National Institutes of Health: $113,060.00
    • National Institutes of Health
    • National Institutes of Health

    ASJC

    • Medicine(all)

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