Anti-Restenotic Roles of Dihydroaustrasulfone Alcohol Involved in Inhibiting PDGF-BB-Stimulated Proliferation and Migration of Vascular Smooth Muscle Cells

Abstract

Dihydroaustrasulfone alcohol (DA), an active compound firstly isolated from marine corals, has been reported to reveal anti-cancer and anti-inflammation activities. These reported activities of DA raised a possible application in anti-restenosis. Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) and the stimulation of platelet-derived growth factor (PDGF)-BB play major pathological processes involved in the development of restenosis. Experimental results showed that DA markedly reduced balloon injury-induced neointima formation in the rat carotid artery model and significantly inhibited PDGF-BB-stimulated proliferation and migration of VSMCs. Our data further demonstrated that translational and active levels of several critical signaling cascades involved in VSMC proliferation, such as extracellular signal-regulated kinase/mitogen-activated protein kinases (ERK/MAPK), phosphatidylinositol 3-kinase (PI3K)/AKT, and signal transducer and activator of transcription (STAT), were obviously inhibited. In addition, DA also decreased the activation and expression levels of gelatinases (matrix metalloproteinase (MMP)-2 and MMP-9) involved in cell migration. In conclusion, our findings indicate that DA can reduce balloon injury-neointimal hyperplasia, the effect of which may be modulated through suppression of VSMC proliferation and migration. These results suggest that DA has potential application as an anti-restenotic agent for the prevention of restenosis.

Constitutive high expression of protein arginine methyltransferase 1 in asthmatic airway smooth muscle cells is caused by reduced microRNA-19a expression and leads to enhanced remodeling

“…In patients with other inflammatory diseases, there is evidence of cross-talk between ERK1/2 MAPK with STAT1 signaling, which results in radical oxygen generation and histone modification. [31][32][33] In addition, ERK1/2 MAPK signaling plays an important role in the regulation of cell proliferation, migration, differentiation, and angiogenesis, suggesting a role for PRMT1 in these events. 34,35 In this study we observed that inhibition of ERK1/2 MAPK suppressed STAT1 phosphorylation, which is consistent with the findings of others.…”

Effect of Paclitaxel+Hirudin on the TLR4-MyD88 Signaling Pathway During Inflammatory Activation of Human Coronary Artery Smooth Muscle Cells and Mechanistic Analysis

“…In addition, secretory smooth muscle cells synthesize and secrete high levels of various cytokines and adhesion molecules, which promote the early occurrence of local inflammatory reactions of the damaged vessel and form an extremely complicated inflammation network control system via the sequential activation of multiple overlapping intracellular signal pathways. Moreover, this process causes the chemotaxis of inflammatory cells and inflammatory cell aggregation and adhesion, aggravates inflammatory reactions, induces local lesion of the vessel, and promotes postintervention restenosis [34,35]. Therefore, further research on inflammation-activated smooth muscle cells is important for the prevention and treatment of restenosis.…”

Rubiarbonone C inhibits platelet‐derived growth factor‐induced proliferation and migration of vascular smooth muscle cells through the focal adhesion kinase, MAPK and STAT3 Tyr705 signalling pathways

“…VSMCs undergo a rapid and reversible change from a quiescent contractile phenotype to a proliferative synthetic phenotype, induced by increased degradation of extracellular matrix proteins, such as gelatin and collagen (Chaabane et al, ). Such decomposition of the extracellular matrix facilitates the induction of VSMC migration (Li et al, ). Phosphorylation of focal adhesion kinase (FAK) has a significant effect on VSMC migration by affecting cytoskeletal remodelling.…”