scholarly journals Effects of compound-326, a selective delta-5 desaturase inhibitor, in ApoE knockout mice with two different protocols for atherosclerosis development

2021 ◽  
Vol 24 ◽  
pp. 71-83
Author(s):  
Hiroki Nagase ◽  
Shuichi Takagahara ◽  
Yoshinori Satomi ◽  
Ayumi Ando ◽  
Kazuki Kubo ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Treatment Protocol ◽  
Atherosclerotic Lesion ◽  
Western Diet ◽  
Intercellular Adhesion Molecule ◽  
Lesion Area ◽  
Apoe Knockout Mice ◽  
Pre Treatment ◽  
Atherosclerosis Development ◽  
Delta 5 Desaturase

Purpose: We previously confirmed its anti-atherosclerotic effects by pre-treatment with compound-326, a selective delta-5 desaturase (D5D) inhibitor, in Western diet-fed ApoE knockout mice. In the present study, we evaluated effects of compound-326 in ApoE knockout mice with two different protocols for atherosclerosis development. Methods: In a post-treatment protocol, where the compound treatment started after 10 weeks pre-feeding of Western diet, compound-326 (1 and 3 mg/kg/day, p.o. for 12 weeks) significantly reduced the atherosclerotic lesion area in the aorta (24% reduction at 3 mg/kg/day). In another protocol using Paigen diet (containing 12.5% cholesterol and 5% sodium cholate), compound-326 (3 and 10 mg/kg/day, p.o. for 7 weeks) also significantly reduced the lesion area (36% reduction at 3 mg/kg/day). Results: In both protocols, Compound-326 significantly reduced the hepatic ratio of arachidonic acid to dihomo-γ-linolenic acid, blood inflammatory eicosanoid production and plasma soluble intercellular adhesion molecule 1 (sICAM-1) levels, similarly to the previous pre-treatment study. Conclusions: Compound-326 exerted anti-atherosclerotic effects in ApoE knockout mice with the two different protocols for atherosclerosis development further supporting D5D inhibition as a promising strategy in treating atherosclerosis.

scholarly journals Western diet feeding influences gut microbiota profiles in apoE knockout mice

2018 ◽  
Vol 17 (1) ◽  
Author(s):  
Baoning Liu ◽  
Yali Zhang ◽  
Rong Wang ◽  
Yingfeng An ◽  
Weiman Gao ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Knockout Mice ◽  
Western Diet ◽  
Apoe Knockout Mice

Abstract 366: Biglycan Deficiency Does Not Affect Angiotensin Ii-induced Atherosclerosis but Promotes Aortic Aneurysms Formation

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Tao Tang ◽  
Joel C Thompson ◽  
Patriticia G Wilson ◽  
Meghan H Yoder ◽  
Lisa R Tannock
Keyword(s):  
Aortic Rupture ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Western Diet ◽  
Aortic Aneurysms ◽  
Lesion Area ◽  
Abdominal Aneurysm ◽  
Aortic Sinus ◽  
Face Surface

Background Proteoglycans play a critical role in the development of atherosclerosis due to their ability to bind and retain atherogenic lipoproteins. Of all the vascular proteoglycans, biglycan has been shown to be the one most closely associated with apolipoprotein B. Our previous studies showed that angII increases vascular biglycan content and predisposes to diet-induced atherosclerosis in Ldlr null mice. The purpose of this study was to determine whether biglycan deficiency protected against angII induced atherosclerosis in vivo. Methods and Results Bgn KO or WT mice, crossed to Ldlr null (C57B/6 background), were infused with angII (1000 ng/kg/min) or saline for 28 days followed by 6-week western diet feeding. Bgn KO mice showed no difference in atherosclerotic lesion area at either aortic sinus or en face surface. Unexpectedly, Bgn KO mice exhibited a striking mortality (77% for males and 48% for females) due to aortic rupture upon angII infusion. Thus, a lower dose of angII was then infused to mice to study atherosclerosis. There was no difference in lesion area between Bgn KO or WT mice under angII (500 ng/kg/min) infusion followed by 6-week western diet feeding or under one-year normal chow feeding without angII infusion. However, angII (500 ng/kg/min) still induced greater aortic rupture in Bgn KO mice (30% for males and 13% for females) than in WT mice (0% for both gender). Besides rupture, 7 Bgn KO mice out of 35 also developed aneurysm at mid-thoracic aorta whereas only 1 Bgn WT mouse out of 25 developed abdominal aneurysm after angII (500 ng/kg/min) infusion. Therefore, our study demonstrated that biglycan deficiency did not affect atherosclerotic lesion development, but induced a striking aneurysm phenotype upon angII infusion.

scholarly journals Comparative Analysis of Luteolin and Luteolin-7-O-Glucoside on anti-Atherogenesis in ApoE Knockout Mice with Hyperhomocysteinemia

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Yeon-A. Son ◽  
Chung-Mu Park ◽  
Youngsun Song
Keyword(s):  
Oxidative Stress ◽  
Adhesion Molecules ◽  
Antioxidative Enzymes ◽  
Adhesion Molecule ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Intercellular Adhesion Molecule ◽  
Control Group ◽  
Apoe Knockout Mice ◽  
And Oxidative Stress

AbstractLuteolin is a naturally occurring flavone that reportedly has anti-inflammatory effect. Flavones in plants are usually present in the form of glucosides, although occasionally they are found as aglycones. The bioavailability of flavones may differ when consumed as either aglycones or glucosides. Nonetheless, numerous studies focused on the biological activity of flavonoid aglycones or that in vitro. These findings are supporting reason to compare the anti-atherogenic effect of aglycone and glucoside forms of flavones in vivo. Male ApoE knockout mice (n = 28, 6-week-old) were divided randomly into 4 groups of 7 mice: negative control group, homocysteine control group, luteolin and luteolin7-O-glucoside groups with homocysteine. All animals were fed by a high-fat diet, modified by AIN-93, containing 0.5% of cholesterol and 45% of fat. Luteolin and luteolin-7-O-glycoside were given daily by gavage for 5 weeks (50 mg/kg BW, respectively). To induce hyperhomocysteinemia, homocysteine was provided as a drinking water (0.9g/L). Administration of homocysteine did not affect body weight gain, feed intake and feed efficiency ratio among groups. Homocysteine feeding sharply increased serum concentrations of homocysteine and triglyceride as well as adhesion molecules including monocyte chemoattractant protein-1 and vascular cell adhesion molecule-1, which were attenuated by the administration of luteolin and luteolin-7-O-glucoside (p < 0.05). Homocysteine administration produced development of atherosclerotic process by the induction of hepatic inducible nitric oxide synthase and cyclooxygenase-2 as well as aortic intercellular adhesion molecule expressions along with diminished expressions of antioxidative enzymes, such as hepatic glutathione reductase (GR), aortic GR and glutathione peroxidase (p < 0.05). Administration of both flavones down-regulated expressions of inflammatory mediators and adhesion molecules as well as up-regulated expressions of antioxidative enzymes (p < 0.05). These data were in accordance with the histopathological observations which were analyzed by hematoxylin and eosin (H&E) stain and immunohistochemistry. In a comparison of both agents, luteolin more potently attenuated inflammation and oxidative stress than luteolin-7-O-glucoside. These results exhibit that luteolin and luteolin-7-O-glycoside ameliorated atherogenic processes through the regulation of inflammation and oxidative stress in ApoE knockout mice with hyperhomocysteinemia. This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government of MOE (No 201704340001).

1.P.79 The effect of lacidipine on atherosclerotic lesion progression in apoE knockout mice

1997 ◽  
Vol 134 (1-2) ◽  
pp. 33 ◽  
Author(s):  
P. Cristofori ◽  
A. Lanzoni ◽  
D. Spagnolo ◽  
L. Cominacini ◽  
A. Pastorino ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Apoe Knockout Mice

HDL is essential for atherosclerotic lesion regression in Apoe knockout mice by bone marrow Apoe reconstitution

2018 ◽  
Vol 278 ◽  
pp. 240-249 ◽  
Author(s):  
Ronald J. van der Sluis ◽  
Robin A.F. Verwilligen ◽  
Zsuzsanna Lendvai ◽  
Robbert Wever ◽  
Menno Hoekstra ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
Apoe Knockout Mice ◽  
Lesion Regression

Postnatal inflammation following intrauterine inflammation exacerbates the development of atherosclerosis in ApoE−/− mice

2019 ◽  
Vol 133 (10) ◽  
pp. 1185-1196 ◽  
Author(s):  
Siroon Bekkering ◽  
Albert P. Limawan ◽  
Maria U. Nguyen ◽  
Lisa K. Widiasmoko ◽  
Hui Lu ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Early Life ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
Chronic Inflammatory Disease ◽  
Mechanistic Studies ◽  
Human Infants ◽  
Size Number ◽  
Severe Atherosclerosis ◽  
Apoe Knockout Mice

Abstract Atherosclerosis is a chronic inflammatory disease that has its origins in early life. Postnatal inflammation exacerbates atherosclerosis, but the possible effect of intrauterine inflammation is largely unexplored. Exposure to inflammation in utero is common, especially in infants born preterm, who have increased cardiovascular risk in adulthood. We hypothesised that exposure to inflammation before birth would accelerate the development of atherosclerosis, with the most severe atherosclerosis following exposure to both pre- and postnatal inflammation. Here we studied the effect of prenatal and postnatal inflammation on the development of atherosclerosis by combining established techniques for modelling histological chorioamnionitis and atherosclerosis using apolipoprotein E (ApoE) knockout mice. A single intra-amniotic (IA) injection of lipopolysaccharide (LPS) caused intrauterine inflammation, and increased atherosclerosis at 13 weeks of postnatal age. In mice exposed to postnatal LPS, chorioamnionitis modulated subsequent responses; atherosclerotic lesion size, number and severity were greatest for mice exposed to both intrauterine and postnatal inflammation, with a concomitant decrease in collagen content and increased inflammation of the atherosclerotic plaque. In conclusion, pre- and postnatal inflammation have additive and deleterious effects on the development of atherosclerosis in ApoE knockout mice. The findings are particularly relevant to preterm human infants, whose gestations are frequently complicated by chorioamnionitis and who are particularly susceptible to repeated postnatal infections. Human and mechanistic studies are warranted to guide preventative strategies.

scholarly journals Low-Cholesterol and High-Fat Diets Reduce Atherosclerotic Lesion Development in ApoE-Knockout Mice

1999 ◽  
Vol 19 (10) ◽  
pp. 2368-2375 ◽  
Author(s):  
Lucía Calleja ◽  
Miguel A. París ◽  
Antoni Paul ◽  
Elisabet Vilella ◽  
Jorge Joven ◽  
...  
Keyword(s):  
Knockout Mice ◽  
Atherosclerotic Lesion ◽  
High Fat ◽  
Lesion Development ◽  
High Fat Diets ◽  
Apoe Knockout Mice ◽  
Fat Diets ◽  
Low Cholesterol ◽  
Atherosclerotic Lesion Development

Circulating levels of the chemokines JE and KC in female C3H apolipoprotein-E-deficient and C57BL apolipoprotein-E-deficient mice as potential markers of atherosclerosis development

2004 ◽  
Vol 32 (1) ◽  
pp. 128-130 ◽  
Author(s):  
S.L. Parkin ◽  
J.P. Pritchett ◽  
D.C. Grimsditch ◽  
K.R. Bruckdorfer ◽  
P.K. Sahota ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Serum Lipids ◽  
Normal Diet ◽  
Western Diet ◽  
Lesion Area ◽  
Atherosclerosis Development ◽  
Circulating Levels ◽  
Deficient Mice ◽  
Oil Red O

We have investigated serum chemokines for their suitability as markers of atherosclerosis development in apoE (apolipoprotein E)-deficient (−/−) mice. Female C3H apoE−/− and C57BL apoE−/− mice were fed on either diet W (Western diet; 6 weeks) or normal rodent diet (12 weeks). Serum lipids (0, 6 and 12 weeks) and terminal chemokine levels were measured using commercially available assays, whereas the lesion area was determined using Oil-Red O-stained aortic sections. Serum lipids were higher in C3H apoE−/− mice for both diets throughout the study; however, lesions were significantly larger in C57BL apoE−/− mice fed on either diet. Chemokine levels were significantly lower in C3H apoE−/− mice fed on the normal diet, but no difference was observed between the two groups fed on diet W. We conclude that serum chemokine levels are potential markers for atherosclerosis susceptibility in C3H and C57BL apoE−/− mice fed on a normal rodent diet.

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