Active polypeptides from Hirudo inhibit endothelial cell inflammation and macrophage foam cell formation by regulating the LOX-1/LXR-?/ABCA1 pathway - 09/06/19
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Graphical abstract |
Highlights |
• | HE (PP) inhibits adhesion and inflammatory response in endothelial cells. |
• | HE (PP) suppresses foam cell formation and apoptosis in macrophages. |
• | HE (PP) inhibits lipid accumulation by regulating LOX-1/LXR-α/ABCA1 pathway. |
• | HE (PP) is identified as a potential novel therapy for atherosclerosis prevention. |
Abstract |
Background and aims |
Hirudo is an important Chinese medicine that has been widely used in patients with thrombosis-related diseases. We aimed to evaluate the protective effect and potential mechanism of Hirudo extract (HE) on the process of atherosclerosis (AS) as well as identify its active components in the lipopolysaccharide (LPS) - or oxidized low-density lipoprotein (ox-LDL)-induced cell models.
Methods |
After treatment, adhesion molecules and pro-inflammatory cytokines induced by LPS were examined by qPCR and ELISA. ROS production, cell apoptosis, and lipid accumulation in ox-LDL-induced cells were analyzed by flow cytometry, qPCR, western blotting, and immunofluorescence staining. In addition, the main active components of HE were identified and analyzed for preventing the progression of AS.
Results |
In this study, we found that HE pretreatment for 48 h significantly inhibited monocyte adhesion and reduced the levels of adhesion factors (ICAM-1 and VCAM-1) and pro-inflammatory factors (IL-6 and TNF-α) in LPS-induced endothelial cells. Moreover, HE attenuated ox-LDL-induced ROS accumulation and apoptosis in macrophage cells via mitochondrial apoptotic pathways. Additionally, HE pretreatment effectively inhibited cholesterol uptake and increased cholesterol efflux by regulating the LOX-1/LXR-α/ABCA1 pathway. Importantly, the polypeptides from HE (PP) with a molecular weight < 10,000 Da accounted for about 62.9% of the total amount of polypeptides, which in turn may be active components of HE that are responsible for inhibiting inflammation, foam cell formation and apoptosis.
Conclusion |
PP from HE potently inhibits endothelial cell inflammatory injury and macrophage foam cell formation and apoptosis by regulating the LOX-1/LXR-α/ABCA1 pathway, thereby providing additional support to the beneficial effects of HE in preventing AS.
El texto completo de este artículo está disponible en PDF.Keywords : Hirudo extract, Polypeptides, Inflammatory response, Foam cell formation, Cholesterol uptake and efflux
Esquema
Vol 115
Artículo 108840- juillet 2019 Regresar al númeroBienvenido a EM-consulte, la referencia de los profesionales de la salud.
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