SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression

Feng, Tao; Liu, Peng; Xiao, Wang; Luo, Jun; Zuo, Xuan; Jiang, Xiaobo; Liu, Chang; Li, Yongzhen; Ni, Li; Chen, Minghua; Zhu, Ning; Han, Xiao; Liu, Chao; Yang, Xu; Si, Shuyi

doi:10.1016/j.atherosclerosis.2018.04.039

Cited by 20 publications

(20 citation statements)

References 49 publications

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“…Next, we investigated the molecular mechanism by which AsC protects against atherosclerosis. Sirt1, a nicotinamide adenine dinucleotide-dependent protein deacetylase, has gained attention for its protective effects against atherosclerosis [45,46]. Excitingly, Sirt1 can modulate macrophage polarization [47] and autophagy [48].…”

Section: Discussionmentioning

confidence: 99%

“…CETSA was performed according to a previous study [26]. Briefly, the cells were collected and heated individually at different temperatures (42,46,50,54,58, and 62°C) for 3 min and then cooled for 3 min at room temperature. Then, the samples were centrifuged, and the obtained cells were analyzed by western blotting.…”

Section: Cellular Thermal Shift Assay (Cetsa)mentioning

confidence: 99%

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Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Luo

Gao

et al. 2020

Aging

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Atherosclerosis-related cardiovascular disease is still the predominant cause of death worldwide. Araloside C (AsC), a natural saponin, exerts extensive anti-inflammatory properties. In this study, we explored the protective effects and mechanism of AsC on macrophage polarization in atherosclerosis in vivo and in vitro. Using a high-fat diet (HFD)-fed ApoE-/-mouse model and RAW264.7 macrophages exposed to ox-LDL, AsC was evaluated for its effects on polarization and autophagy. AsC significantly reduced the plaque area in atherosclerotic mice and lipid accumulation in ox-LDL-treated macrophages, promoted M2 phenotype macrophage polarization, increased the number of autophagosomes and modulated the expression of autophagy-related proteins. Moreover, the autophagy inhibitor 3-methyladenine and BECN1 siRNA obviously abolished the antiatherosclerotic and M2 macrophage polarization effects of AsC. Mechanistically, AsC targeted Sirt1and increased its expression, and this increase in expression was associated with increased autophagy and M2 phenotype polarization. In contrast, the effects of AsC were markedly blocked by EX527 and Sirt1 siRNA. Altogether, AsC attenuates foam cell formation and lessens atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Cellular Thermal Shift Assay (Cetsa)mentioning

confidence: 99%

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Luo

Gao

et al. 2020

Aging

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“…We then tested the protein expression of CRLR/RAMPs and found only RAMP3 protein level elevated in VDNtreated old aortas, by 3.5-fold (P<0.01) as compared with VDN-treated young aortas, and by 1.7-fold (P<0.01) as compared with old control aortas ( Figure 1L-1P). We tested IMD expression in rat replicative senescent VSMCs (passage [14][15][16][17][18] and found decreased expression of IMD mRNA, and that of its receptors, CRLR/RAMP2/3 proteins, was increased, as compared with young VSMCs (passage 3-6) (Supplementary Figure 1A-1E).…”

Section: Imd and Its Receptor Levels In Aging-associated Vascular Calmentioning

confidence: 99%

“…Sirt1 is a well-known longevity factor: it can extend the lifespan of yeast, Caenorhabditis elegans and flies and delay the aging process of mammals [12,13]. Sirt1 is highly expressed in the vasculature and protects against age-related cardiovascular diseases, including cardiac remodeling [14,15], atherosclerosis [16], abdominal aortic aneurysm [17], and vascular calcification [8,9]. Recent study demonstrated that cultured aortas of mice with sirt1 knockdown showed accelerated medial calcification induced by inorganic phosphate [18].…”

Section: Introductionmentioning

confidence: 99%

Intermedin1-53 attenuates aging-associated vascular calcification in rats by upregulating sirtuin 1

Chen

Zhang

Ren

et al. 2020

Aging

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Vascular calcification is a common phenomenon in older adults. Intermedin (IMD) is a cardiovascular bioactive peptide inhibiting vascular calcification. In this study, we aimed to investigate whether IMD1-53 attenuates aging-associated vascular calcification. Vascular calcification was induced by vitamin D3 plus nicotine (VDN) in young and old rats. The calcification in aortas was more severe in old rats treated with VDN than young control rats, and IMD expression was lower. Exogenous administration of IMD1-53 significantly inhibited the calcium deposition in aortas and the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) in VDNtreated old rats. Moreover, levels of aging-related p16, p21 and β-galactosidase were all greatly decreased by IMD1-53. These results were further confirmed in rat and human VSMCs in vitro. In addition, IMD-deficient mouse VSMCs showed senescence features coinciding with osteogenic transition as compared with wild-type mouse VSMCs. Mechanistically, IMD1-53 significantly increased the expression of the anti-aging factor sirtuin 1 (sirt1); the inhibitory effects of IMD1-53 on calcification and senescence were blocked by sirt1 knockdown. Furthermore, preincubation with inhibitors of PI3K, AMPK or PKA efficiently blunted the upregulatory effect of IMD1-53 on sirt1. Consequently, IMD1-53 could attenuate aging-associated vascular calcification by upregulating sirt1 via activating PI3K/Akt, AMPK and cAMP/PKA signaling.

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“…Sirtuin 1 (SIRT1) plays an additional protective role in vascular biology and atherosclerosis (Stein & Matter, 2011). It has anti‐inflammatory functions that disrupt the NF‐κB signaling pathway, downregulating the expression of various pro‐inflammatory cytokines in endothelial cells and macrophages (Feng et al., 2018). A previous study reported that SIRT1 overexpression in transgenic mice inhibited NF‐κB activity induced by high‐fat foods and reduced specific pro‐inflammatory cytokines, including TNFα and IL‐6, promoting fatty liver (Pfluger et al., 2008).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of phenethyl isothiocyanate on foam cell formation by combined treatment of oxidized low‐density lipoprotein and lipopolysaccharide in THP‐1 macrophage

Gwon

Yun

2021

Food Science & Nutrition

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Accumulation of cholesterol‐laden macrophage foam cells characteristic of early stage atherosclerotic lesions. Phenethyl isothiocyanate (PEITC) is a naturally occurring isothiocyanate found in cruciferous vegetables that has reported a variety of activities including antioxidant and anti‐inflammatory properties. However, the protective effect of PEITC on foam cell formation and its precise mechanism is not yet clear. Therefore, we investigated whether PEITC suppresses foam cell formation and regulates the expression of genes related to lipid accumulation, cholesterol efflux, and inflammation in THP‐1 derived‐macrophages. We exposed THP‐1 derived‐macrophages to oxidized low‐density lipoprotein (ox‐LDL) (20 μg/mL) and lipopolysaccharide (LPS) (500 ng/ml) to mimic foam cell formation. Here, PEITC downregulated the expression of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1), cluster of differentiation 36 (CD36), scavenger receptor A1 (SR‐A1), and nuclear factor‐κB (NF‐κB), while upregulated ATP binding cassette subfamily A member 1 (ABCA1)/liver‐X‐receptor α (LXR‐α)/peroxisome proliferator‐activated receptor gamma (PPARγ) and sirtuin 1 (SIRT1) expression compared to co‐treated with ox‐LDL and LPS. Taken together, PEITC, at least in part, inhibits foam cell formation and reduces lipid accumulation in foam cells. Therefore, we suggest that PEITC may be a potential candidate for the treatment and prevention of vascular inflammation and atherosclerosis.

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SIRT1 activator E1231 protects from experimental atherosclerosis and lowers plasma cholesterol and triglycerides by enhancing ABCA1 expression

Cited by 20 publications

References 49 publications

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Araloside C attenuates atherosclerosis by modulating macrophage polarization via Sirt1-mediated autophagy

Intermedin1-53 attenuates aging-associated vascular calcification in rats by upregulating sirtuin 1

Protective effects of phenethyl isothiocyanate on foam cell formation by combined treatment of oxidized low‐density lipoprotein and lipopolysaccharide in THP‐1 macrophage

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