Eicosapentaenoic acid and docosahexaenoic acid selectively attenuate U46619-induced smooth muscle cell proliferation

It is well known that vascular smooth muscle cell (SMC) proliferation is a key step in atheromatous plaque formation. Thromboxane A2 (TxA2), released from aggregating platelets and an injured vessel wall, may play an important role in the development of atheromatous plaque. Many animal studies have suggested that n-3 polyunsaturated fatty acids eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) present in the fish oils have antiatherosclerotic effects. In the present study, we investigated the effect of EPA and DHA on TxA2-induced SMC proliferation. To determine the functional selectivity of n-3 fatty acids, we also tested the effect of arachidonic acid (AA, 20:4n-6), gamma-linolenic acid) (LNA, 18:3n-6), and oleic acid (OA, 18:1n-9) on TxA2-induced SMC proliferation. Only EPA and DHA prevented the SMC proliferation induced by the TxA2 mimetic U46619. When EPA and DHA were added together in the ratio in which they are present in menhaden oil, EPA and DHA acted synergistically to block the SMC proliferation induced by the TXA2-mimetic. These findings suggest that the n-3 polyunsaturated fatty acids in fish oils may exert antiatherosclerotic effects by blocking the mitogen-stimulated proliferation of SMC.