Selective conversion and esterification of monohydroxyeicosatetraenoic acids by human vascular smooth muscle cells: relevance to smooth muscle cell proliferation.
5-, 12-, and 15-hydroxyeicosatetraenoic acid (HETE), lipoxygenase metabolites of arachidonic acid that may modulate cell proliferation, were examined for their ability to affect the [3H]thymidine incorporation of human umbilical artery smooth muscle cells. We found that these hydroxy fatty acids inhibited the serum-induced [3H]thymidine incorporation of growth-arrested vascular smooth muscle cells in a similar dose-dependent manner. The inhibitory effect was dependent on the serum concentration used to stimulate cell growth. The higher the serum concentration, the lower the inhibitory effect of the HETE. In parallel experiments, the incorporation of HETEs into lipids of the smooth muscle cells was examined. After 20 h of incubation, we found that in the presence of 0.4% serum 70% of 3H-labeled 5-HETE was esterified into human vascular smooth muscle cell lipids. Twelve and eight percent, respectively, of 12- and 15-HETE were incorporated into smooth muscle cell lipids. Furthermore, we found that during the 20-h incubation of human umbilical artery smooth muscle cells with 12- and 15-HETE, these compounds were converted into metabolites with a chromatographic behavior on HPLC similar to that of diHETEs. 5-HETE was not converted into these polar metabolites. Increasing the serum concentration resulted in a decreased metabolism of all HETEs tested. Thus, the distinct differences between the metabolism of different HETEs by vascular smooth muscle cells does not reflect the proliferation inhibitory effect of these HETEs.