Journal of Lipid Research, Vol 31, 329-334, Copyright © 1990 by Lipid Research, Inc.
Effects of phorbol 12-myristate 13-acetate on triglyceride and cholesteryl ester synthesis in cultured coronary smooth muscle cells and macrophages
M Moinat, JM Chevey, P Muzzin, JP Giacobino and M Kossovsky
Departement de Biochimie Medicale, Centre Medical Universitaire, Geneve, Switzerland.
In cultured pig coronary smooth muscle cells phorbol 12-myristate 13-
acetate (PMA) stimulated the conversion of [4-14C]cholesterol into
cholesteryl esters and the incorporation of [2-3H]glycerol into
triglycerides 6.4- and 4.5-fold, respectively. The maximal effects occurred
after 3 h of treatment and there was a return to basal values after 72 h.
In the presence of 400 microM oleic acid, PMA stimulated the conversion of
[4-14C]cholesterol into cholesteryl esters and that of [2-3H]glycerol into
triglycerides 5.3- and 2.3-fold, respectively. The stimulatory effects were
more sustained (still significant after 72 h) and their maxima were delayed
(peaks after 24 h). PMA was also found to increase 2-fold the amount of
triglyceride that accumulated in the cells in the presence of oleic acid
after 24 h. In macrophages IC-21, the effects of PMA were observed only in
the presence of oleic acid. They consisted of a 1.9-fold stimulation in the
conversion of [4- 14C]cholesterol into cholesteryl esters after 72 h and of
a 1.7-fold stimulation in the incorporation of [2-3H]glycerol into
triglycerides after 24 h. PMA also increased the amount of triglyceride
that accumulated in the cells 1.9-fold after 72 h. It is concluded that
PMA, and possibly growth factors, may promote lipid storage in smooth
muscle cells and that fatty acids favor long lasting effects of PMA in
smooth muscle cells and are necessary for any effect of PMA in macrophages.