Astragaloside IV inhibits platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells via the inhibition of p38 MAPK signaling

Abstract

Astragaloside IV (AS-IV), the major active component extracted from Astragalus membranaceus, has been demonstrated to exhibit protective effects on the cardiovascular, immune, digestive and nervous systems; thus, has been widely used in traditional Chinese medicine. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) is closely associated with the initiation and progression of cardiovascular diseases, including atherosclerosis and restenosis. However, the effects of AS-IV on VSMCs remain unknown. For the first time, the present study demonstrated that AS-IV markedly suppressed platelet-derived growth factor (PDGF)-BB-stimulated cellular proliferation and migration of HDMEC-a human dermal VSMCs (HDVSMCs). Further investigation into the underlying molecular mechanisms demonstrated that the administration of AS-IV attenuated the PDGF-BB-stimulated switch of HDVSMCs into a proliferative phenotype. Furthermore, AS-IV inhibited the PDGF-BB-induced expression of cell cycle-associated proteins, as well as the upregulation of matrix metalloproteinase (MMP)2, but not MMP9. In addition, AS-IV was shown to downregulate the activation of p38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB in HDVSMCs. Therefore, the observations of the present study indicate that AS-IV inhibits PDGF-BB-stimulated VSMC proliferation and migration, possibly by inhibiting the activation of the p38 MAPK signaling pathway. Thus, AS-IV may be useful for the treatment of vascular diseases.

Alisol A 24-Acetate, a Triterpenoid Derived from <b><i>Alisma orientale</i></b>, Inhibits Ox-LDL-Induced Phenotypic Transformation and Migration of Rat Vascular Smooth Muscle Cells through Suppressing ERK1/2 Signaling

“…Such a process is the early stage of atherosclerosis, while VSMC migration and the subsequent formation of foam cells is the later process for the formation of atherosclerotic plaque. Phenotypic transformation is considered as a critical process for VSMC proliferation and migration [22]. In this study, the phenotypic transformation and migration ability of Ox-LDL-treated VSMCs was found to be higher than that in the blank control group, which was in agreement with the results from other studies.…”

Suppressive effect of formononetin on platelet-derived growth factor-BB-stimulated proliferation and migration of vascular smooth muscle cells

“…Herein, it was reported that formononetin suppressed PDGF-BB-stimulated VSMCs proliferation. Furthermore, the results indicate that PDGF-BB could induce VSMCs to dedifferentiate into a proliferative phenotype, as suggested by the downregulation of SMA, smoothelin and desmin, which is consistent with previous studies (16,24). However, treatment with formononetin attenuated the PDGF-BB-induced downregulation of SMA, smoothelin and desmin, indicating that formononetin inhibited the PDGF-BB-induced phenotype change in VSMCs.…”

“…Cell cycle-related proteins, including CDK2, CDK4, cyclin D1 and cyclin E, are crucially involved in the regulation of cell cycle progression, as well as cell proliferation (16). It has been reported that formononetin has effects on the expression of cell cycle-related proteins (8).…”

Decreased S100A9 Expression Promoted Rat Airway Smooth Muscle Cell Proliferation by Stimulating ROS Generation and Inhibiting p38 MAPK

“…p38 MAPK signaling pathway is significantly inhibited by PDGF-induced proliferation in smooth muscle cells. For example, astragaloside IV inhibits PDGF-stimulated proliferation by inhibiting p38 MAPK in human vascular smooth muscle cells [16]. p38 MAPK activation is also required for the esculetin-induced inhibition of vascular smooth muscle cell proliferation [17].…”