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 μM) 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.
Highlights
Atherosclerosis (AS) is a major pathological disease for cardiovascular and cerebrovascular problems and the most common disease in the cardiovascular system [1]
vascular endothelial cell (VEC) survival rates in glucose concentrations of 5.5 and 15.5 mM increased in a dose- and time-dependent manner
Compared with the single cultured group, vascular smooth muscle cell (VSMC) in the coculture group proliferated significantly (P < 0.05), which suggested that injured VECs stimulated VSMCs proliferation (Figure 3). These results showed that VSMC proliferation stimulated by high glucose injured VECs was even much stronger than that stimulated directly by high glucose
Summary
Atherosclerosis (AS) is a major pathological disease for cardiovascular and cerebrovascular problems and the most common disease in the cardiovascular system [1]. Diabetes mellitus is considered as an important risk factor to the accelerated atherosclerosis [3,4,5]. High glucose has been shown to injure vascular endothelial cells (VECs) and vascular smooth muscle cells (VSMCs), which are two important cells of artery wall and responsible for AS progression [6]. VEC inflammatory injury and dysfunction are initial factors, and VSMC proliferation and migration are key pathological features [7,8,9]. VSMCs are tightly associated with VECs in structure and function. VECs dysfunction will release cytokines like VEGF, bFGF, TGF-β, and PDGF which have shown regulatory effects on VSMC proliferation and migration
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