ROLE OF FATTY ACID BINDING PROTEIN IN CARDIAC ISCHEMIA

Project: Research project

Project Details

Description

The research goal is to study the role of fatty acid binding protein
(FABP), in fatty acid metabolism in the normal, ischemic and hypoxic heart
as an example of the molecular basis of cellular injury. Fatty acids and
their metabolites have been implicated in membrane damage and enzyme
inhibition during ischemia secondary to their amphipathic nature. They are
also thought to be arrhythmogenic. The objective of study is to test the
hypothesis that FABP has a critical role in fatty acid metabolism, and that
under ischemic conditions, failure of binding of fatty acids to FABP due to
decreased systhesis, increased destruction or altered cellular conditions
is the critical event leading to an increase in cytosolic unbound fatty
acids and their toxic metabolism. Phase I will be devoted to isolating and
characterizing cardiac FABP, developing antibodies to establish and
Enzyme-Linked Immunosorbent Assay (ELISA), and studying the localization
and turnover of FABP in the heart. During Phase II the function of FABP
under normal, hypoxic and ischemic conditions will be studied in the
working isolated perfused heart and in vivo. Coronary occlusion in the
anesthetized, open-chested rabbit will be used as the in vivo model and
plasma and myocardial tissue FABP levels will be measured by the ELISA
assay developed in Phase I. This work will provide new information about
the underlying molecular events which precipitate arrhythmias and the
biochemistry of myocardial ischemia. The second goal of this proposal is
for the PI to learn basic biochemical skills including the development and
application of immunologic methodologies under the direction of an
established biochemist.
StatusFinished
Effective start/end date4/1/873/31/92

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $75,330.00

ASJC

  • Medicine(all)

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