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AJP - Cell Physiology, Vol 264, Issue 4 C885-C893, Copyright © 1993 by American Physiological Society
ARTICLES |
L. L. Stoll and A. A. Spector
Department of Anesthesia, University of Iowa, Iowa City 52242.
Lysophosphatidylcholine (lyso-PC) is a vasoactive phospholipid present in oxidized low-density lipoprotein. We used a coculture model of the vascular wall to study its interaction with endothelial cells (EC) and vascular smooth muscle cells (SMC). Lyso-PC was taken up readily by SMC and gradually acylated to phosphatidylcholine. Low concentrations (< or = 1 microM) of lyso-PC present in the interstitial medium of an EC-SMC coculture system were taken up primarily by the SMC. Lyso-PC produced a rapid two- to three-fold increase in SMC guanosine 3',5'-cyclic monophosphate (cGMP) levels, reaching a maximum in 1 min. This increase was associated with decreased SMC proliferation and increased calcium influx. The increase in intracellular calcium was inhibited by verapamil and KT5823, a specific cGMP-dependent kinase inhibitor, while a similar increase was produced by the membrane-permeant cGMP analogue 8-bromoguanosine 3',5'-cyclic monophosphate. These studies suggest that SMC are the primary target for the biological effects of lyso-PC present in the vessel wall and that the responses are mediated by calcium influx, possibly due to opening of a verapamil-sensitive cGMP kinase-dependent channel.
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