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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:3481-3488.)
© 1997 American Heart Association, Inc.

Articles

HDL-Induced Prostacyclin Release in Smooth Muscle Cells Is Dependent on Cyclooxygenase-2 (Cox-2)

M. Viñals; J. Martínez-González; J. J. Badimon; ; L. Badimon

From the Cardiovascular Research Centre, CSIC-H. Sant Pau-UAB, Barcelona, Spain, and the Cardiovascular Institute, Mount Sinai Medical Center, New York, USA (J.J.B.).

Correspondence to Lina Badimon, Laboratori d'Investigació-Cardiovascular, Hospital de la Santa Creu i Sant Pau, Avda. San Antoni Maria Claret No. 167, 08025 Barcelona, Spain. E-mail lbmucv{at}cid.csic.es

Abstract Cyclooxygenase-1 (Cox-1) and Cox-2 are key enzymes in the conversion of arachidonic acid to prostaglandins and other eicosanoids. We studied the effects of plasma HDL and LDL on the synthesis of prostacyclin, Cox-1/Cox-2 mRNA, and protein expression by rabbit aortic smooth muscle cells. Prostacyclin synthesis was measured by enzyme immunoassay (EIA) of the stable metabolite of prostacyclin (PGI₂), 6-keto-prostaglandin F₁. HDL (150 µg/mL) induced release of PGI₂ to values 3.46±0.3-fold above control. Incubations with LDL did not induce release of PGI₂. N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide (NS-398), a selective irreversible Cox-2 inhibitor, blocked the HDL-induced PGI₂ synthesis. Cycloheximide, actinomycin D, and dexamethasone downregulated HDL-induced PGI₂ synthesis; therefore, HDL induced de novo synthesis of protein and Cox-2 mRNA. In addition, Northern blot analyses did not reveal differences in Cox-1 mRNA levels between control and HDL-treated cells, whereas Cox-2 mRNA levels were significantly increased in treated cells. Western blot analysis also showed an increase in the levels of Cox-2 protein. Therefore, the effects of HDL on PGI₂ synthesis are mediated via upregulation of Cox-2 expression.

Key Words: HDL • LDL • cyclooxygenase-1 • cyclooxygenase-2 • NS-398

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