Pelargonidin attenuates PDGF-BB-induced aortic smooth muscle cell proliferation and migration by direct inhibition of focal adhesion kinase

Abstract

Pelargonidin is a natural red pigment found in fruits and vegetables, and has been reported to exhibit various effects potentially beneficial for human health. However, the possible preventive effects of pelargonidin toward atherosclerosis and mechanisms involved have not been investigated to date. Here, we compared the effects of pelargonidin and its glucoside-conjugated form, pelargonidin-3-glucoside (P3G), on proliferation and migration induced by platelet-derived growth factor (PDGF)-BB in human aortic smooth muscle cells (HASMCs). Pelargonidin, but not P3G, exhibited strong inhibitory effects against PDGF-BB-induced HASMC proliferation and migration, while suppressing PDGF-BB-induced ex vivo rat aortic ring sprouting. Immunoblot analysis revealed that pelargonidin inhibited PDGF-BB-induced phosphorylation of focal adhesion kinase (FAK) as well as F-actin reduction, whereas Src, mitogen-activated protein kinases (MAPKs) and Akt phosphorylation status were not altered. We also observed that the anti-proliferative and migratory effects of both pelargonidin and P3G corresponded with the extent of FAK inhibition. Both in vitro and ex vivo pull-down assays revealed that pelargonidin binds directly with FAK in an adenosine triphosphate-competitive manner, suggesting that FAK could be a molecular target of pelargonidin. Interestingly, pelargonidin did not exhibit inhibitory effects on the proliferation, migration or FAK phosphorylation of human umbilical vein endothelial cells (HUVECs). Taken together, our results suggest that pelargonidin exhibits potential preventive effects toward atherosclerosis through the attenuation of HASMC proliferation and migration, as well as aortic sprouting via the direct inhibition of FAK activity.

Keywords: Aortic smooth muscle cells; Atherosclerosis; Focal adhesion kinase; Pelargonidin; Pelargonidin chloride (Pubchem CID: 67249); Pelargonidin-3-O-glucoside chloride (Pubchem CID: 16218556).