(Circulation. 2000;102:1874.)
© 2000 American Heart Association, Inc.
Editorial |
Matrix Matters
From Brigham and Women’s Hospital and Harvard Medical School, Boston, Mass.
Correspondence to Peter Libby, MD, Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital, 221 Longwood Ave, LMRC 307, Boston, MA 02115. E-mail plibby@rics.bwh.harvard.edu
Key Words: Editorials • extracellular matrix • metalloproteinases • cells
Cardiologists have commonly conceived of the extracellular matrix as an inert collection of structural macromolecules that serve as a scaffold for cells. Rapidly accumulating evidence challenges this view. Matrix macromolecules can regulate key functions of cells, and the composition of the cardiovascular extracellular matrix is under strict control. These control mechanisms can act in a slow and almost imperceptible manner, causing long-term changes in tissue structure, but they can also be very rapid, facilitating almost immediate changes in cellular behavior. Here, we explore these new concepts in the context of certain common cardiovascular diseases.
Extracellular Matrix Can Control Cell Behavior
A large body of evidence supports a central role of the
extracellular matrix in the control of numerous cellular functions
(Table
). Extracellular matrix molecules can ligate integrin
molecules on the surface of cardiac myocytes,
endothelial cells, and smooth muscle cells, as well as
inflammatory cells that participate in important
cardiovascular diseases. On ligation, integrin
receptors can transduce signals that alter key cellular functions
("outside-in signaling").1 Cells bound to different
extracellular matrix substrates through integrins respond differently
to growth factors and other stimuli. In the absence of signals arising
from attachment to the extracellular matrix, cells can undergo
apoptosis. A number of growth factors bind to extracellular
matrix molecules, conferring biochemical stability to the growth
factors and serving as a tissue reservoir of mitogens primed for
release. Proteoglycans can function at the cell surface as coreceptors
for growth factors like fibroblast growth factor-22 or
within the interstitial space, where proteoglycans like
versican and biglycan can bind
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