scholarly journals Idebenone protects against atherosclerosis in apolipoprotein E-deficient mice via activation of the Sirt3-SOD2-mtROS pathway

2020 ◽  
Author(s):  
Wei Jiang ◽  
Hongzhi Geng ◽  
Xiaoqing Lv ◽  
Jing Ma ◽  
Pengfei Lin ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Apolipoprotein E ◽  
Cell Damage ◽  
Density Lipoprotein ◽  
Control Group ◽  
Atherosclerotic Plaques ◽  
High Dose ◽  
Protective Agent ◽  
Deficient Mice ◽  
Progression Of Atherosclerosis

Abstract Background: Atherosclerosis, which is a form of chronic aortic disease, results from the accumulation and aggregation of oxidized low density lipoprotein（LDL）in the vessel walls, the development of neointima, the formation of a fibrous cap, and the migration of immune cells to the damaged vascular endothelium. Recent studies have shown that mitochondrial function is closely associated with the development and progression of atherosclerosis. Idebenone functions as an electron carrier and antioxidant, and previous studies have shown that it effectively clears oxygen-free radicals. In the current study, we demonstrate that idebenone could protect against atherosclerosis using apolipoprotein E-deficient mice. Methods: High-fat diet（HFD）and idebenone treatment with apolipoprotein E-deficient mice . A total of 60 mices were randomized into the following four groups: (1) HFD (2) idebenone-low dose (3) idebenone-medium dose and (4) idebenone-high dose for 16 weeks. The HUVECs were pretreated with endothelial cell medium in the presence or absence of 0.2 mM idebenone working solution for 3 h followed by exposure to 10 μM cholesterol for 24 h. Proteomics analysis was performed between the HFD group (n=3) and the high-dose idebenone group (n=3, concentration = 400 mg/kg/d).Results: Compared with the HFD group, Idebenone can suppresses the formation of atherosclerotic plaques and increases the stability of atherosclerotic plaques in apoE-/- mice; Compared with the control group, Idebenone can protects against endothelial cell damage and inhibits the production of mtROS in cholesterol mediated HUVECs; Idebenone could effectively inhibit the development and progression of atherosclerosis and the injury of endothelial cells through the SIRT3-SOD2-mtROS pathway.Conclusions: We showed that idebenone could act as a mitochondrial protective agent during the development and progression of atherosclerosis by inhibiting the activation of NLPR3 via the SIRT3-SOD2-mtROS pathway. Idebenone may be a promising therapy for patients with atherosclerosis in the future, as it can improve mitochondrial dysfunction and inhibit oxidative stress.

Perinatal Administration of C-Phycocyanin Protects Against Atherosclerosis in apoE-Deficient Mice by Modulating Cholesterol and Trimethylamine-N-Oxide Metabolisms

2021 ◽  
Author(s):  
Marine Coué ◽  
Mikael Croyal ◽  
Marina Habib ◽  
Blandine Castellano ◽  
Audrey Aguesse ◽  
...  
Keyword(s):  
Bile Acid ◽  
Apolipoprotein E ◽  
Lithocholic Acid ◽  
Adult Life ◽  
Density Lipoprotein ◽  
Female Offspring ◽  
Control Group ◽  
Liver Gene ◽  
Atherosclerosis Development ◽  
Deficient Mice

Objective: Gestational hypercholesterolemia concomitantly with a highly oxidative environment is associated with higher atherosclerosis in human and animal offspring. This work aimed to determine whether perinatal administration of a C-phycocyanin concentrate, a powerful antioxidant, can protect against atherosclerosis development in genetically hypercholesterolemic mice in adult life. Approach and Results: C-Phycocyanin was administered during gestation solely or gestation and lactation to apolipoprotein E-deficient mice. Male and female offspring were studied until 25 weeks old. Progenies born to supplemented mothers displayed significantly less atherosclerotic root lesions than control group in all groups excepted in male supplemented during gestation and lactation. Female born to supplemented mothers had a greater gallbladder total bile acid pool, lower secondary hydrophobic bile acid levels such as lithocholic acid, associated with less plasma trimethylamine N -oxide at 16 weeks old compared with control mice. Regarding male born to C-Phycocyanin administrated mothers, they expressed a higher high-density lipoprotein cholesterol level, more soluble bile acids such as β-muricholic acids, and a decreased plasma trimethylamine at 16 weeks old. Liver reduced-to-oxidized glutathione ratio were increased and liver gene expression of superoxide dismutase and glutathione peroxidase were significantly decreased in male born to gestational supplemented mothers. No difference in the composition of cecal microbiota was found between groups, regardless of sex. Conclusions: Our findings suggest a protective effect of perinatal antioxidant administration on atherosclerosis development in apolipoprotein E-deficient mice involving sex-specific mechanisms.

scholarly journals High-Dose Recombinant Apolipoprotein A-IMilanoMobilizes Tissue Cholesterol and Rapidly Reduces Plaque Lipid and Macrophage Content in Apolipoprotein E–Deficient Mice

Circulation ◽  
2001 ◽  
Vol 103 (25) ◽  
pp. 3047-3050 ◽  
Author(s):  
Prediman K. Shah ◽  
Juliana Yano ◽  
Odette Reyes ◽  
Kuang-Yuh Chyu ◽  
Sanjay Kaul ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
High Dose ◽  
Apolipoprotein A ◽  
Tissue Cholesterol ◽  
Deficient Mice

scholarly journals Evaluation of Lipid Lowering Effect of Milk Thistle (Silybum Marianum) in Comparison with Rosuvastatin in Rats by Using Ace-alera® Analyzer

2020 ◽  
Vol 14 ◽  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Lipid Lowering ◽  
Control Group ◽  
Milk Thistle ◽  
High Dose ◽  
Hypolipidemic Effect ◽  
Low Density ◽  
Therapeutic Protocols

Dyslipidemia is a metabolic disorder that is characterized with an elevation in the cholesterol serum levels that can be treated with various hypolipidemic drugs like rosuvastatin. The present study was undertaken to determine and evaluate the hypolipidemic effect of milk thistle seeds extract in comparison with rosuvastatin and the combination of both for the treatment of dyslipidemia in rats. Also its effect on blood glucose levels on experimentally induced dyslipidemic rats. In vivo studies were conducted on wister albino laboratory rats, in which 49 rats were induced to be dyslipidemic by a daily intragastric administration of cholesterol (2 g/kg). The induction of dyslipidemia was evaluated by comparing these rats with a negative control group that was composed of 10 healthy rats. Then, after one month dyslipidemia was induced in 49 rats that were divided into 6 groups, as the following; positive control group (n=9) received cholesterol (2 g/kg) for another one month, and the other five groups each of 8 rats continued to receive cholesterol (2 g/kg) for one month along with therapy as; rosuvastatin low dose (RL) group received 10 mg/kg, rosuvastatin high dose (RH) group received 20 mg/kg, milk thistle (MT) group received 7.15 mg/kg, (RL+MT) group received a combination of 10 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle, and (RH+MT) group received a combination of 20 mg/kg of rosuvastatin and 7.15 mg/kg of milk thistle. The statistical results of biochemical analysis showed that all the studied therapeutic protocols whether given alone; RL, RH, and MT or in a combination; RL+MT and RH+MT led to a significant (p≤0.05) hypolipidemic effect that reduced the total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL) and very low density lipoprotein (VLDL) and increased the high density lipoprotein (HDL) cholesterol levels. In conclusion, all therapeutic protocols were effective in treating dyslipidemia, as they all reduced the TC, TG, LDL, and VLDL, and increased the HDL cholesterol significantly (p≤0.05). Furthermore, we found that milk thistle can be used in the management of dyslipidemia, as it has a hypolipidemic effect. Also, the addition of milk thistle to rosuvastatin therapy reduced the risk of developing diabetes mellitus (DM), as it has a glucose modulating activity either when it was given alone or in combination with rosuvastatin. Moreover, the combination of milk thistle and rosuvastatin was of a great benefit, as it gave an intensive goal of therapy than each one alone in altering all lipid profile parameters.

scholarly journals Deficiency of Glutathione Peroxidase-1 Accelerates the Progression of Atherosclerosis in Apolipoprotein E-Deficient Mice

2007 ◽  
Vol 27 (4) ◽  
pp. 850-857 ◽  
Author(s):  
Michael Torzewski ◽  
Viola Ochsenhirt ◽  
Andrei L. Kleschyov ◽  
Matthias Oelze ◽  
Andreas Daiber ◽  
...  
Keyword(s):  
Glutathione Peroxidase ◽  
Apolipoprotein E ◽  
Glutathione Peroxidase 1 ◽  
Deficient Mice ◽  
Progression Of Atherosclerosis

Abstract 236: Sirt6 Heterozygosity Exacerbates Atherosclerosis in Apolipoprotein E Deficient Mice

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
De-Pei Liu ◽  
Zhu-Qin Zhang ◽  
Si-Cong Ren ◽  
Zuo-Zhi Li ◽  
Ying Tan ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Apolipoprotein E ◽  
Histone Deacetylase ◽  
Epigenetic Modification ◽  
Atherosclerotic Plaques ◽  
Nkg2d Ligand ◽  
Class Iii ◽  
Ligand Expression ◽  
Atherosclerosis Development ◽  
Deficient Mice

Sirt6 is a member of the class III histone deacetylase family and is reported to promote longevity. Whether Sirt6 is involved in atherosclerosis, one aging associated disease and the major cause of cardiovascular diseases, is unknown. We investigated effects of Sirt6 on atherosclerosis development. We found that in human atherosclerotic plaques, Sirt6 expression was decreased. Sirt6+/-ApoE-/- mice exhibited increased atherosclerosis development and decreased plaque stability than ApoE-/- mice. We found that Sirt6 downregulation showed increased expression of NKG2D ligands (H60b in mice and MICA/B in human). Sirt6 bound to promoters of these genes and regulated the H3K9 acetylation levels. Thus, atherosclerosis development was promoted by Sirt6 heterozygosity and epigenetic modification of NKG2D ligand expression is involved in this process.

scholarly journals The Endogenous Estradiol Metabolite 2-Methoxyestradiol Reduces Atherosclerotic Lesion Formation in Female Apolipoprotein E-Deficient Mice

Endocrinology ◽  
2007 ◽  
Vol 148 (9) ◽  
pp. 4128-4132 ◽  
Author(s):  
Johan Bourghardt ◽  
Göran Bergström ◽  
Alexandra Krettek ◽  
Sara Sjöberg ◽  
Jan Borén ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Low Dose ◽  
Hormone Replacement ◽  
Atherosclerotic Lesion ◽  
Total Serum ◽  
High Dose ◽  
Lesion Formation ◽  
Cholesterol Levels ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Formation

Estradiol, the major endogenous estrogen, reduces experimental atherosclerosis and metabolizes to 2-methoxyestradiol in vascular cells. Currently undergoing evaluation in clinical cancer trials, 2-methoxyestradiol potently inhibits cell proliferation independently of the classical estrogen receptors. This study examined whether 2-methoxyestradiol affects atherosclerosis development in female mice. Apolipoprotein E-deficient mice, a well-established mouse model of atherosclerosis, were ovariectomized and treated through slow-release pellets with placebo, 17β-estradiol (6 μg/d), or 2-methoxyestradiol [6.66 μg/d (low-dose) or 66.6 μg/d (high-dose)]. After 90 d, body weight gain decreased and uterine weight increased in the high-dose but not low-dose 2-methoxyestradiol group. En face analysis showed that the fractional area of the aorta covered by atherosclerotic lesions decreased in the high-dose 2-methoxyestradiol (52%) but not in the low-dose 2-methoxyestradiol group. Total serum cholesterol levels decreased in the high- and low-dose 2-methoxyestradiol groups (19%, P < 0.05 and 21%, P = 0.062, respectively). Estradiol treatment reduced the fractional atherosclerotic lesion area (85%) and decreased cholesterol levels (42%). In conclusion, our study shows for the first time that 2-methoxyestradiol reduces atherosclerotic lesion formation in vivo. The antiatherogenic activity of an estradiol metabolite lacking estrogen receptor activating capacity may argue that trials on cardiovascular effects of hormone replacement therapy should use estradiol rather than other estrogens. Future research should define the role of 2-methoxyestradiol as a mediator of the antiatherosclerotic actions of estradiol. Furthermore, evaluation of the effects of 2-methoxyestradiol on cardiovascular disease endpoints in ongoing clinical trials is of great interest.

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