Abstract 5879: Vascular Smooth Muscle Cells Express ErbB Receptors and Migrate In Response to Neuregulin
It is currently believed that in the heart only endothelial cells express the ligand of erbB receptors neuregulin-1 (NRG, a member of the EGF family). We previously demonstrated that NRG leads to angiogenesis in vivo. To determine whether other vascular cells express this ligand-receptor system and what role they may play in the angiogenic response, primary human coronary artery smooth muscle cells (HCASMC, passages 6 –11) were immunoblotted for erbB1, erbB2, erbB3, erbB4 and NRG. All 4 erbB receptors were present in proliferating SMC, with erbB3 being the least highly expressed. The NRG protein expressed by HCASMC has a slightly different molecular weight compared to that expressed by HUVEC-derived endothelial cells, suggesting that HCASMC may express different NRG isoforms than those found in endothelium. ErbB receptor stimulation by NRG has been shown to lead to activation of ERK and/or AKT signaling pathways in a pattern that is dependent on the types of erbB receptors expressed, the cell type, and the isoform of NRG used. To understand which signaling pathways are activated by NRG in SMC, HCASMC underwent a treatment time course with 2 different NRG isoforms: NRG alpha and NRG beta3. NRG alpha stimulation resulted in the rapid (5–15 min) activation of ERK 1/2 and AKT (SER473). NRG beta3 also activated ERK 1/2 but not AKT. Finally we examined whether activating HCASMC with NRG promotes cell migration. In a modified Boyden chamber assay, stimulation with NRG alpha doubled the number of HCASMC that migrated versus the control (P<0.05). However, NRG beta3 had no effect on migration, suggesting that AKT activation may play a critical role in smooth muscle migration in response to NRG-erbB signaling. These novel findings suggest that in the heart, vascular SMC may also be important players in NRG/erbB activated vascular responses.