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The Role of Integrins in Vascular Cell Signaling and Regulation of
Vascular Tone and Permeability
APS Cell and Molecular Physiology Section
Michael J. Davis
G.A. Meininger, J. Bhattacharya, S. Chien and G. E. Davis
Integrins are a large
family of membrane-spanning glycoproteins that link the extracellular matrix
(ECM) to the cytoskeleton. Integrins mediate both 'inside-out' and
'outside-in' signaling by virtue of their role in the organization and
assembly of cytoskeletal signaling complexes within the focal adhesion.
These complexes contain a large number of cytoskeletal proteins, adaptor
proteins and protein tyrosine kinases that, when assembled or rearranged,
initiate downstream signaling cascades. Integrin interactions with soluble
and insoluble ECM ligands can trigger these intracellular signaling events
but, in addition, integrins provide paths for preferential transduction of
mechanical force across the plasma membrane. The role of integrins in the
adherence, differentiation, migration and growth of cells in the
cardiovascular system, e.g. in angiogenesis, is well known. But recently,
there is emerging evidence that integrins also play an important role in the
acute regulation of vascular tone and vascular permeability under both
physiological and pathophysiological conditions. The premise of this
symposium is to highlight and discuss the evidence for these previously
unappreciated roles for integrins in blood vessels.
The symposium will begin
with a brief introduction by the Chair, Dr. M. Davis, to the concept of
integrin-mediated mechanotransduction and signaling in the vasculature. Dr.
Meininger will then present evidence that soluble integrin ligands can
acutely regulate vascular tone, and discuss recently developed methods for
measuring integrin-specific mechanotransduction in vascular cells using
atomic force microscopy. Dr. Bhattacharya will focus on the role of
integrins in regulating the endothelial permeability barrier in lung
capillaries. Dr. Chien will discuss the role of integrins in the
mechanotransduction of shear stress to endothelium. Finally, Dr. G. Davis
will introduce novel ideas about how breakdown of the ECM, as occurs in
vascular remodeling, ischemic injury and a number of other pathological
conditions, can expose cryptic sites in ECM proteins (matricryptins),
allowing them to play a role in the acute regulation of vascular tone. It is
anticipated that presentation and discussion of these new roles for
integrins in vascular endothelium and smooth muscle will be a topic of great
interest to members of the APS and other societies and will stimulate new
avenues of cardiovascular research.
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