Effects of the prostanoids on the proliferation or hypertrophy of cultured murine aortic smooth muscle cells

1 Effects of the prostanoids on the growth of cultured aortic vascular smooth muscle cells (VSMCs) were examined using mice lacking prostanoid receptors. 2 Proliferation of VSMCs was assessed by measuring [H-3]-thymidine incorporation and the cell number, and their hypertrophy by [C-14]-leucine incorporation and protein content. 3 In VSMCs from wild-type mice, expressions of mRNAs for the EP4 and TP were most abundant, followed by those for the IP, EP3 and FP, when examined by competitive reverse transcriptase-PCR. Those for the EP1, EP2 and DP, however, could not be detected. 4 AE1-329, an EP4 agonist, and cicaprost, an IP agonist, inhibited platelet derived growth factor proliferation of VSMCs from wild-type mice; these inhibitory effects disappeared completely in VSMCs from EP4-/- and IP-/- mice, respectively. In accordance with these effects, AE1-329 and cicaprost stimulated cAMP production in VSMCs from wild-type mice, which were absent in VSMCs from EP4-/- and IP-/- mice, respectively. 5 Effects of PGE(2) on cell proliferation and adenylate cyclase were almost similar with those of AE1-329 in VSMCs from wild-type mice, which disappeared in VSMCs from EP4-/- mice. 6 PGD(2) inhibited PDGF-induced proliferation of VSMCs from both wild-type and DP-/- mice to a similar extent. This action of PGD(2) was also observed in VSMCs from EP4(-/-) and IP-/- mice. 7 In VSMCs from wild-type mice, I-BOP, a TP agonist, showed potentiation of PDGF-induced hypertrophy. I-BOP failed to show this action in VSMCs from TP-/- mice. 8 The specific agonists for the EP1, EP2 or EP3, and PGF(2)alpha showed little effect on the growth of VSMCS. 9 These results show that PGE(2), PGI(2) and TXA(2) modulate PDGF-induced proliferation or hypertrophy of VSMCs via the EP4, IP and TP, respectively, and that the inhibitory effect of PGD(2) on PDGF-induced proliferation is not mediated by the DP, EP4 or IP.