Free fatty acids (FFA)
are the major source of energy for the heart. Normal
cardiac function therefore requires an adequate and
constant supply of FFA, which is obtained from the blood
that supplies the heart. The heart must efficiently
transport the FFA from the blood, across the heart cell
membranes and into the cytoplasm where the FFA can be
used for the energy needed to drive heart muscle.
Kleinfeld,
Carley and Kampf's
laboratory uses the novel techniques, akin to the
ones untilized with type II diabetes research, to
investigate how FFA are transported across the heart
cell membranes. To do this, their laboratory has isolated
individual heart cells, microinjected these cells
with a fluorescent indicator of FFA and used quantitative
fluorescent microscopy to monitor FFA transport in
living heart cells. The results that are obtained
are similar to those in adipocytes, suggesting that
heart cells have mechanisms for taking up as well
as releasing FFA.
Although the heart requires sufficient quantities
of FFA for normal function, too much FFA may be deleterious.
In collaboration with FFA Sciences, Dr. Kleinfeld's
lab has developed fluorescent indicators that can
specifically detect the portion of FFA in blood that
is soluble in the water phase of plasma, the unbound
FFA (FFAu). The investigations indicate that in acute
cardiovascular disease, blood levels of FFAu may increase
as much as 100 fold above normal. FFAu elevations
occur very early in acute cardiac events (ischemia)
and may therefore provide an early indicator of a
heart attack. Moreover, the lab's studies of heart
attack patients demonstrate that elevated FFAu levels
at the earliest times are prognostic for immediate
(hours to days) risk of death. These studies raise
the possibility that the FFAu themselves may mediate
the deleterious effects and suggest that therapies
that rapidly lower FFAu levels might reduce deaths
due to myocardial infarctions.
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