Abstract
Vascular smooth muscle cell (SMC) migration and proliferation contribute to arterial wound repair and thickening of the intimal layer in atherosclerosis. SMC can physically interact with monocytes and macrophages within the intima. This study evaluated whether macrophages modulated proliferation and migration of SMC in close proximity, which was suppressed by 1—25 μg/ml sensitive fern (Onoclea sensibilis) extract (SFE) inhibiting protein-tyrosine phosphatase-1B activity. The addition of conditioned media of THP-1-derived macrophages substantially promoted human aortic smooth muscle cell (HAoSMC) proliferation by ≈30%. HAoSMC proliferation was significantly attenuated by ≥10 μg/ml SFE most likely due to its diminution of platelet derived growth factor (PDGF)-BB secreted by neighbor macrophages. HAoSMC migration was also enhanced by culturing in THP-1 macrophage conditioned media, as evidenced by a scratch wound assay. However, the presence of ≥10 μg/ml SFE did not allow such migaration. When SFE was treated to THP-1 macrophages, the secretion of the adipokines, visfatin and resistin, was abrogated. SFE at 1—25 μg/ml dose-dependently diminished resistin-stimulated secretion of collagen IV and connective tissue growth factor (CTGF) in HAoSMC, indicating that macrophage resistin plays a role in the extracellular matrix (ECM) production of vascular SMC. These results demonstrate that SFE disturbed proliferation and migration of SMC instigated by inflammatory macrophages in close proximity. Therefore, this study provides novel information that SFE has the potential capability to prevent atherosclerosis involving SMC proliferation, migration and fibrogenic activation within the vessels.
