P74 Retinoids inhibit vascular smooth muscle cell proliferation in vitro and intimal hyperplasia in vivo in rats. We examined the underlying mechanism of the antiproliferative effect of retinoids on human coronary smooth muscle cells (CASMC). The retinoids tested included: RAR ligands, all-trans retinoic acid (atRA) and Ethyl-p-[(E)-2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthyl)-l-propenyl]-benzoic acid (TTNPB); a RXR and RAR ligand 9-cis retinoic acid (9cRA); and the potent RXRα- ligand AGN4204. All retinoids inhibited DNA synthesis in CASMC stimulated with platelet derived growth factor and insulin (IC 50 : TTNPB 0.063μM, atRA 0.123μM, AGN4204 0.461μM, 9cRA 1.529μM, all p -7 M; AGN4204 and 9cRA, 2x10 -6 M all p -9 M; atRA, 2x10 -7 M; AGN4204, 2x10 -6 M, all p Kip1 , a major negative regulator of G1 cyclin/CDK activity (maximal effect: TTNPB and atRA, 2x10 -7 M; AGN4204 and 9cRA, 2x10 -6 M, all p