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.
Highlights
Balloon angioplasty-induced restenosis is characterized by platelet aggregation, the release of growth factors, inflammation, abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) within the media layer of arterial wall, and extracellular matrix (ECM) remodelling
We examined the effects of Dihydroaustrasulfone alcohol (DA) on Platelet-derived growth factor (PDGF)-BB-induced proliferation of VSMCs by using MTT assay
The manifestation of vascular restenosis was presented as the ratio of neointima-to-media area (N/M ratio); (B) The distribution and expression of proliferating cell nuclear antigen (PCNA) protein were detected with immunohistochemistry analysis, and the images were acquired by microscopy at 400× magnification; (C) The distribution and expression of signal transducer and activator of transcription 3 (STAT3) protein were detected with immunohistochemistry analysis, and the images were acquired by microscopy at 400× magnification
Summary
Balloon angioplasty-induced restenosis is characterized by platelet aggregation, the release of growth factors, inflammation, abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) within the media layer of arterial wall, and extracellular matrix (ECM) remodelling. Among these events, VSMC proliferation and migration have been believed to play a critical role involved in the development of atherosclerosis and restenosis [1,2]. Soft coral-derived natural marine compounds, such as Capnellene and lemnalol, have been shown to attenuate the chronic constriction injury-induced neuropathic pain and inflammatory/analgesic effects [11,12]. VSMCs proliferation and migration as well as balloon injury-induced neointimal hyperplasia
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.