Store-operated Ca(2+) entry is not essential for PDGF-BB induced phenotype modulation in rat aortic smooth muscle

Suppression of smooth muscle cell (SMC) differentiation marker genes is central to SMC phenotype modulation during vasculo-proliferative diseases such as atherosclerosis and restenosis. Upregulation of the intermediate-conductance Ca(2+)-activated K(+) channel (K(Ca)3.1) is integral for mitogen-induced suppression of SMC marker genes and post-angioplasty restenosis. Modulation of SMC marker gene expression has been observed following Ca(2+) influx from multiple sources, however, it is unknown whether upregulation of K(Ca)3.1 and/or suppression of SMC differentiation genes is dependent on a Ca(2+) mediated mechanism. The purpose of this study was to determine the dependence of mitogen-induced SMC phenotype modulation on store-operated Ca(2+) entry (SOCE). In growth-arrested, differentiated rat aortic SMCs, platelet-derived growth factor-BB (PDGF-BB) augmented SOCE. However, PDGF-BB induced upregulation of K(Ca)3.1 and downregulation of the SMC marker gene smooth muscle myosin heavy chain (SMMHC) and myocardin was not dependent on SOCE. Co-treatment with the iPLA2 inhibitor bromoenol lactone (BEL) inhibited the effects of PDGF-BB on SMC phenotype modulation and SOCE. Our results indicate SOCE is not required for PDGF-BB induced phenotype modulation in rat aortic SMCs. Rather, we implicate a novel BEL-sensitive mechanism which regulates both SOCE and phenotype modulation, independently.