Luteolin Inhibits Smooth Muscle Cell Migration and Proliferation by Attenuating the Production of Nox4, P-Akt and VEGF in Endothelial Cells
Hong Ding, Dongye Li, Yanbin Zhang, Tian Zhang, Hong Zhu, Tongda Xu, Yuanyuan Luo and Cheng WangAffiliation:
Institute of Cardiovascular Research and Department of Cardiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China.
AbstractObjective: The goals of this study were to observe how luteolin protects endothelial cells (ECs) from injury stimulated by Angiotensin II (Ang II), investigate the role of vascular endothelial dysfunction in vascular smooth muscle cell proliferation and migration in vitro and investigate its primary mechanism of action. Methods: A non-contact coculture system was established using a transwell system; ECs were cultured in the lower wells, while the smooth muscle cells (SMCs) were cultured in the upper wells. Cell proliferation was assessed by the MTT assay. The number of SMCs that migrated through the membrane of transwell system were observed and counted. The expression levels of various proteins (VEGF, p-Akt, Nox4) expressed in ECs were determined by Western blotting. VEGF mRNA expression was detected by reverse transcription-polymerase chain reaction (RT-PCR). The supernatants of ECs were measured by enzyme linked immunosorbent assay (ELISA) to assay VEGF concentration. Results: Ang II-stimulated ECs significantly increased the proliferation and migration of SMCs, and these effects were inhibited by luteolin pretreatment. Luteolin suppressed the Ang II-induced upregulation of Nox4, p-AKT and VEGF expression in ECs. Conclusion: These results demonstrate that luteolin is capable of inhibiting endothelial dysfunction induced by Ang II by suppressing the upregulation of Nox4, p-Akt and VEGF, thereby restraining the proliferation and migration of SMCs induced by injured ECs.
Angiotensin II, endothelial cells, luteolin, proliferation and migration, smooth muscle cells, vascular endothelial growth factor.
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