title: Paeonol Inhibits Proliferation of Vascular Smooth Muscle Cells Stimulated by High Glucose via Ras-Raf-ERK1/2 Signaling Pathway in Coculture Model.
abstract: Paeonol (Pae) has been previously reported to protect against atherosclerosis (AS) by inhibiting vascular smooth muscle cell (VSMC) proliferation or vascular endothelial cell (VEC) injury. But studies lack how VSMCs and VECs interact when Pae plays a role. The current study was based on a coculture model of VSMCs and VECs to investigate the protective mechanisms of Pae on atherosclerosis (AS) by determining the secretory function of VECs and proliferation of VSMCs focusing on the Ras-Raf-ERK1/2 signaling pathway. VECs were stimulated by high glucose. Our data showed that high concentration (35.5 mM) of glucose induced damage in VECs. Injury of VECs stimulated VSMC proliferation in the coculture model. Pae (120  μ M) decreased vascular endothelial growth factor (VEGF) and platelet derivative growth factor B (PDGF-B) release from VECs and inhibited overexpression of Ras, P-Raf, and P-ERK proteins in VSMCs. The results indicate that diabetes modulates the inflammatory response in VECs to stimulate VSMC proliferation and promote the development of AS. Pae was beneficial by inhibiting the inflammatory effects of VECs on VSMC proliferation. This study suggests the inhibitory mechanism of Pae due to the inhibition of VEGF and PDGF-B secretion in VECs and Ras-Raf-ERK1/2 signaling pathway in VSMCs.
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China ; School of Pharmacy, Anhui University of Traditional Chinese Medicine, Shihe Road 45, Hefei, Anhui 230031, China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
authors.affiliation: Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Traditional Chinese Medicine, Hefei 230038, China.
authors.forename: Yueqin
authors.initials: Y
authors.lastname: Wang