Antimitogenic effects of prostacyclin on the G1 phase cyclin-dependent kinases

The prostanoid prostacyclin (PGI(2)) inhibits proliferation of cultured vascular SMCs by inhibiting cell cycle progression from G1 to S phase. Progression through G1 phase is regulated by the sequential activation of the G1 phase cycl in-dependent kinases (cdks). Recent studies have shown that PGI(2)-dependent activation of its receptor, 1P, inhibits G1 phase progression by blocking the degradation of p27 and the activation of cyclin E-cdk2. High Density Lipoproteins (HDL) and its associated apolipoprotein, ApoE, also inhibit S phase entry of vascular SMCs, and the effects of HDL and ApoE are, at least in part, also mediated by the production of PGI(2). The antimitogenic effects of hyaluronan may also be controlled by PGI(2). This review summarizes the effects of PGI(2) on the G1 phase cyclin-cdks and discusses the potential role of PGI(2) as a common component of multiple extracellular signals that attenuate the proliferation of vascular SMCs. (c) 2005 Elsevier Inc. All rights reserved.