Chen Pin-Yu, Lin Mao-Shin, Chen Chin-Chuan, Leu Yann-Lii, Wang Shu-Huei
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
J Nutr Biochem. 2025 Jan;135:109771. doi: 10.1016/j.jnutbio.2024.109771. Epub 2024 Sep 18.
Abnormal vascular smooth muscle cell (VSMC) proliferation and migration play crucial roles in neointimal hyperplasia and restenosis progression in response to stimulation with various inflammatory cytokines, such as platelet-derived growth factor-BB (PDGF-BB) and tumour necrosis factor-α (TNF-α). Hydroxygenkwanin (HGK) exerts remarkable anti-inflammatory, antitumour, antiproliferative and antimigratory effects. The aim of the study was to elucidate the therapeutic effect and regulatory mechanism of HGK on neointimal hyperplasia. The results showed that HGK inhibited the abnormal proliferation, migration, and inflammation of PDGF-BB- or TNF-α-treated VSMCs through regulation of the PDK1/AKT/mTOR pathway. In addition, HGK promoted circulating endothelial progenitor cell (EPC) chemotaxis. In an in vivo assay, HGK dramatically enhanced re-endothelization and reduced neointimal hyperplasia after femoral artery denudation with a guide wire in mice. These results suggest that HGK can serve as a therapeutic target drug or a functional food supplement for the treatment of restenosis.
异常的血管平滑肌细胞(VSMC)增殖和迁移在对各种炎性细胞因子(如血小板衍生生长因子-BB(PDGF-BB)和肿瘤坏死因子-α(TNF-α))刺激的反应中,在新生内膜增生和再狭窄进展中起关键作用。羟基关附素(HGK)具有显著的抗炎、抗肿瘤、抗增殖和抗迁移作用。本研究的目的是阐明HGK对新生内膜增生的治疗作用和调节机制。结果表明,HGK通过调节PDK1/AKT/mTOR途径抑制PDGF-BB或TNF-α处理的VSMC的异常增殖、迁移和炎症。此外,HGK促进循环内皮祖细胞(EPC)趋化。在体内试验中,HGK显著增强了小鼠股动脉用导丝剥脱后的再内皮化并减少了新生内膜增生。这些结果表明,HGK可作为治疗再狭窄的治疗靶点药物或功能性食品补充剂。