Control of smooth muscle cell proliferation in vascular disease.
OBJECTIVE
Smooth muscle cell proliferation has previously been regarded as a central feature in vascular disease. The role of this process has recently been substantially re-evaluated, and we have reconsidered the functional importance of smooth muscle cell proliferation, the origin of proliferating smooth muscle cells in lesions, and the mechanisms whereby smooth muscle cell proliferation is controlled. In this review, we summarize recent progress in the understanding of smooth muscle cell proliferation, with a particular focus on how interactions between the extracellular matrix, smooth muscle cells, and mitogens control critical steps in this process.


RESULTS
Irrespective of the origin of smooth muscle cells in vascular lesions, fundamental interactions between the extracellular matrix and cell surface integrins are necessary in order to initiate a proliferative response in a quiescent smooth muscle cell, in a similar manner to any non-malignant cell. These interactions trigger intracellular signaling and cell cycle entry, which facilitate cell cycle progression and proliferation by mitogens. In addition, extracellular matrix interactions may also control the availability and activity of growth factors such as heparin-binding mitogens, which can be sequestered by heparan sulfate containing extracellular matrix components and regulate smooth muscle cell proliferation.


CONCLUSIONS
New insights into mechanisms whereby the extracellular matrix takes part in the control of smooth muscle cell proliferation suggest a number of putative targets for future therapies that can be applied to increase plaque stability, prevent the clinical consequences of atherosclerosis and improve outcomes after interventional procedures and organ transplantation.
Hedin
Ulf
U
Department of Surgical Sciences, Karolinska Hospital, Stockholm, Sweden. ulf.hedin@kirugi.ki.se
Roy
Joy
J
Tran
Phan-Kiet
PK
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009130:Muscle, Smooth / Q000166:cytology* / Q000473:pathology