Inhibition of LOXL1-AS1 alleviates oxidative low-density lipoprotein induced angiogenesis via downregulation of miR-590-5p mediated KLF6/VEGF signaling pathway

Cell Cycle ◽  
2021 ◽  
pp. 1-18
Author(s):  
Xuan Cheng ◽  
Zhiwei Liu ◽  
Haifeng Zhang ◽  
Yajun Lian
2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Aijun Sun ◽  
Xueting Jin ◽  
Jingjing Zhao ◽  
Keqiang Wang ◽  
Fang Xu ◽  
...  

Aims: Probucol, an agent characterized by lipid-lowering and anti-oxidant property, retards atherosclerosis effectively. Our study aimed to test the hypothesis that probucol might act its anti-athersclerotic role by suppressing maturation of human monocyte-derived dendritic cells (h-monDC). Furthermore, we also used a LDLR-/- mice model fed a high-fat diet to detect whether probucol also perform its anti-atherosclerotic effect on suppressing DCs maturation in vivo. Methods: H-monDCs were derived by incubating purified human monocytes with GM-CSF and IL-4. H-monDCs were pre-incubated with or without probucol and stimulated by oxidized low-density lipoprotein (ox-LDL) in the presence or absence of heme oxygenase (HO-1) siRNA. In vivo studies, streptozotocin (STZ) induced LDLR-/- mice were fed either a high-fat (HF) diet or added with 0.5% probucol for 4 months. Expression of h-monDC membrane molecules and mice splenic CD11c+DC membrane molecules were analyzed by FACS, cytokines were measured by ELISA and the STAT1/CIITA associated signaling pathway was determined by Western blotting. Mice aortic lesions were observed by En face staining and the expression of CD11c+DCs within atherosclerotic plaques were shown under confocal microscopy. Results: Ox-LDL promoted h-monDC maturation and TNF-a production; and up-regulated STAT1 701 phosphorylation by activating HO-1 in STAT1/CIITA signaling pathway. These effects were inhibited by probucol. Knocking down HO-1 with specific siRNA blocked these effects of probucol. In LDLR-/- mice fed a high-fat diet, probucol treatment significantly regressed aortic atherosclerotic lesions, suppressed splenic CD11c+DCs maturation and IL-12p70 production; and resulted in absence of CD11c+DCs within atherosclerotic lesions. Conclusions: Our study indicated that probucol effectively suppressed maturation of h-monDC induced by ox-LDL through HO-1 activation, and retarded atherosclerosis at least partly through inhibiting maturations of CD11c+DCs in LDLR-/- mice.


1996 ◽  
Vol 271 (32) ◽  
pp. 19251-19255 ◽  
Author(s):  
Nathalie Augé ◽  
Nathalie Andrieu ◽  
Anne Nègre-Salvayre ◽  
Jean-Claude Thiers ◽  
Thierry Levade ◽  
...  

2021 ◽  
Author(s):  
Wenping Guo ◽  
Hongguang Jin ◽  
Yiqiang Wang ◽  
Yongsheng Huang ◽  
Xing Zhu ◽  
...  

Abstract Recombinant hirudin (r-hirudin) has a good anticoagulant effect and also has a certain inhibitory effect on atherosclerosis (AS), however, its intrinsic mechanism of inhibiting AS is still unclear. In this study, we investigated the mechanism underlying the vascular and myocardial protective effects of r-hirudin in AS rats through animal experiments. A rat AS model was established by high-fat diet feeding combined with common carotid artery balloon injury. The model rats were given low, medium, or high doses of r-hirudin (0.05, 0.1, or 0.2 mg/kg/day), simvastatin tablets (1 mg/kg/day) and p38 mitogen-activated protein kinase (MAPK) pathway inhibitors (SB203580, 100 mg/kg/day) by gavage for 8 weeks. The results showed that in AS rats, r-hirudin significantly alleviated pathological changes in the common carotid artery and myocardial tissue; decreased serum total cholesterol (TC), triglyceride (TG) and low-density lipoprotein-cholesterol (LDL-C) levels; increased high-density lipoprotein-cholesterol (HDL-C) levels; decreased serum oxidized low-density lipoprotein (ox-LDL), tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and endothelin (ET)-1 levels; increased nitric oxide (NO) levels; and decreased p38 MAPK, nuclear factor-kappa B (NF-κB), caspase-9, caspase-3 mRNA and protein expression. This study showed that r-hirudin may protect blood vessels and the myocardium in AS rats by adjusting blood lipid levels and inhibiting the p38 MAPK/NF-κB signaling pathway to exert anti-inflammatory and anti-apoptotic effects and protect the vascular endothelium.


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