Abstract
Cell proliferation and migration of vascular smooth muscle (VSM) cells in diabetes mellitus (DM) is promoted possibly by 1) autonomous activation of their stimulatory signal transductions, 2) autonomous inhibition of their inhibitory signal transductions, 3) autocrine stimulation by growth factors or 4) enhanced responsiveness to growth factors. To answer this question, cell proliferation and migration of cultured aortic VSM cells derived from type 2 DM model OLETF rats and from normal LETO rats (OVSMC and LVSMC) was compared in different culture condition.: serum-free DMEM (SFM), 10% FBS-DMEM or SFM containing platelet-derived growth factor-BB (SFM-PDGF). In addition, we examined whether elevation of intracellular cAMP by olprinone hydrochloride (OPN), an inhibitor for type 3 phosphodiesterase (PDE), inhibits cell proliferation and migration. As compared with LVSMC, cell proliferation and migration of OVSMC were significantly increased in SFM and 10%FBS-DMEM, but not in SFM-PDGF. Exposure of OVSMC and LVSMC to OPN (1 mM), dibutyryl-cAMP (3 mM) or dibutyryl-cGMP (3 mM) for 72 hr significantly inhibited PDGF-BB (2 nM)-induced cell proliferation and migration. Intracellular cAMP was significantly increased by OPN in both OVSMC and LVSMC. In conclusion, cell proliferation and migration of VSM cells in type 2 DM might be autonomously enhanced, which could be regulated by elevation of intracellular cAMP and cGMP. [J Physiol Sci. 2008;58 Suppl:S201]
