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.

scholarly journals Perinatal Hypercholesterolemia Exacerbates Atherosclerosis Lesions in Offspring by Altering Metabolism of Trimethylamine-N-Oxide and Bile Acids

2017 ◽  
Vol 37 (11) ◽  
pp. 2053-2063 ◽  
Author(s):  
Charlotte Trenteseaux ◽  
Anh-thu Gaston ◽  
Audrey Aguesse ◽  
Guillaume Poupeau ◽  
Pierre de Coppet ◽  
...  
Keyword(s):  
Gene Expression ◽  
Apolipoprotein E ◽  
Bile Acids ◽  
Experimental Studies ◽  
Underlying Mechanism ◽  
Female Offspring ◽  
Promoter Regions ◽  
Maternal Hypercholesterolemia ◽  
Atherosclerosis Development ◽  
Deficient Mice

Objective— Experimental studies suggest that maternal hypercholesterolemia may be relevant for the early onset of cardiovascular disease in offspring. We investigated the effect of perinatal hypercholesterolemia on the atherosclerosis development in the offspring of apolipoprotein E–deficient mice and the underlying mechanism. Approach and Results— Atherosclerosis and related parameters were studied in adult male or female apolipoprotein E–deficient mice offspring from either normocholesterolemic or hypercholesterolemic mothers and normocholesterolemic fathers. Female born to hypercholesterolemic mothers had more aortic root lesions than female born to normocholesterolemic mothers. Lesions in whole aorta did not differ between groups. Higher trimethylamine-N-oxide levels and Fmo3 hepatic gene expression were higher in female born to hypercholesterolemic mothers offspring compared with female born to normocholesterolemic mothers and male. Trimethylamine-N-oxide levels were correlated with the size of atherosclerotic root lesions. Levels of hepatic cholesterol and gallbladder bile acid were greater in male born to hypercholesterolemic mothers compared with male born to normocholesterolemic mothers. At 18 weeks of age, female born to hypercholesterolemic mothers showed lower hepatic Scarb1 and Cyp7a1 but higher Nr1h4 gene expression compared with female born to normocholesterolemic mothers. Male born to hypercholesterolemic mothers showed an increase in Scarb1 and Ldlr gene expression compared with male born to normocholesterolemic mothers. At 25 weeks of age, female born to hypercholesterolemic mothers had lower Cyp7a1 gene expression compared with female born to normocholesterolemic mothers. DNA methylation of Fmo3, Scarb1 , and Ldlr promoter regions was slightly modified and may explain the mRNA expression modulation. Conclusions— Our findings suggest that maternal hypercholesterolemia may exacerbate the development of atherosclerosis in female offspring by affecting metabolism of trimethylamine-N-oxide and bile acids. These data could be explained by epigenetic alterations.

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 Anti-atherogenic effect of soya and rice-protein isolate, compared with casein, in apolipoprotein E-deficient mice

2003 ◽  
Vol 90 (1) ◽  
pp. 13-20 ◽  
Author(s):  
Weihua Ni ◽  
Yasuyuki Tsuda ◽  
Shinichiro Takashima ◽  
Hiroyoshi Sato ◽  
Masao Sato ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Lesion Size ◽  
Protein Isolate ◽  
Plant Proteins ◽  
Male Mice ◽  
Lesion Area ◽  
Rice Protein ◽  
Water Drinking ◽  
En Face ◽  
Deficient Mice

Our objective was to determine whether dietary plant proteins such as soya-protein isolate (SPI) and rice-protein isolate (RPI) compared with animal proteins, such as casein, could afford beneficial effects on atherosclerosis development in apolipoprotein E-deficient mice. In experiment 1, male and female mice were fed on a purified diet containing either casein, SPI or RPI for 9 weeks. The en face lesion area in the aorta (P < 0·05) and the lesion size in the aortic root (P < 0·05) in mice fed the casein-based diet were greater than those in the SPI or RPI groups. The plant protein groups had an increased concentration of serum l-arginine (P < 0·05) and NO metabolites (NO2 plus NO3) (P < 0·05) than did the casein group. The inhibitory effect of the plant proteins on the lesion formations was unrelated to gender and total serum cholesterol. In experiment 2, the l-arginine and l-methionine contents were the same in the l-arginine-supplemented casein-based and SPI-based diets, and between the l-methionine-supplemented SPI-based and the casein-based diets. Male mice were fed on the diets for 15 weeks. There were no significant differences in the en face lesion area and the lesion size between the casein group and the l-arginine-supplemented group, although the serum l-arginine (P < 0·05) and NO2 plus NO3 (P < 0·05) concentrations in the supplemented group were higher than those in the casein group. There were no significant effects of l-methionine supplementation on the lesion formations. In experiment 3, male mice were given the casein-based diet or the l-arginine-supplemented casein-based diet together with water or water containing an NO synthesis inhibitor for 9 weeks. When given the casein-based diet, the inhibitor drinking, compared with water drinking, resulted in a reduction of the serum NO2 plus NO3 concentration (P < 0·01) and an increase in the en face lesion area (P < 0·05) and the lesion size (P < 0·01). When given the l-arginine-supplemented diet, the inhibitor drinking, compared with water drinking, resulted in no increase in the lesion area and size. These results demonstrate anti-atherogenic potentials of SPI- as well as RPI-derived proteins, but their l-arginine and l-methionine contents were not sufficient enough to explain the underlying mechanism(s).

Milk-Derived Peptides, Val-Pro-Pro and Ile-Pro-Pro, Attenuate Atherosclerosis Development in Apolipoprotein E–Deficient Mice: A Preliminary Study

2013 ◽  
Vol 16 (5) ◽  
pp. 396-403 ◽  
Author(s):  
Teppei Nakamura ◽  
Tatsuhiko Hirota ◽  
Katsura Mizushima ◽  
Kohji Ohki ◽  
Yuji Naito ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Preliminary Study ◽  
Atherosclerosis Development ◽  
Deficient Mice

scholarly journals Flavonols reduce aortic atherosclerosis lesion area in apolipoprotein E deficient mice: A systematic review and meta-analysis

PLoS ONE ◽  
2017 ◽  
Vol 12 (7) ◽  
pp. e0181832 ◽  
Author(s):  
James Phie ◽  
Smriti M. Krishna ◽  
Joseph V. Moxon ◽  
Safraz M. Omer ◽  
Robert Kinobe ◽  
...  
Keyword(s):  
Systematic Review ◽  
Apolipoprotein E ◽  
Meta Analysis ◽  
Aortic Atherosclerosis ◽  
Lesion Area ◽  
Deficient Mice

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.

ADAMTS13 Reduces Vascular Inflammation and Early Development of Atherosclerosis Via VWF-Dependent Mechanism.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2178-2178
Author(s):  
Chintan Gandhi ◽  
Steven R. Lentz ◽  
Anil K Chauhan
Keyword(s):  
Vascular Inflammation ◽  
Inflammatory Cells ◽  
Neutrophil Infiltration ◽  
Western Diet ◽  
High Fat ◽  
Lesion Area ◽  
Aortic Sinus ◽  
The Mean ◽  
Deficient Mice ◽  
Early Atherosclerosis

Abstract Abstract 2178 Background and objective: The metalloprotease ADAMTS13 prevents spontaneous thrombosis in the microvasculature by cleaving hyperactive ultra large von Willebrand factor (ULVWF) multimers into smaller and less active forms. Recently, we and others have demonstrated that ADAMTS13-deficiency aggravates vascular inflammation and early atherosclerosis in apolipoprotein E-deficient (ApoE−/−) mice fed a high-fat Western diet. Although VWF is the only known substrate for ADAMTS13, it is not known if the effects of ADAMTS13 on vascular inflammation and atherosclerosis are mediated through its proteolytic effects on VWF or possibly another ADAMTS13 substrate. In this study, we determined whether the exacerbated atherosclerosis observed in the Adamts13−/−/ApoE−/− mice is dependent or independent of VWF. Model and methods: ApoE−/−, Adamts13−/−/ApoE−/−, Adamts13−/−/Vwf−/−/ApoE−/− and Vwf−/−/ApoE−/− male mice were fed a high-fat Western diet (20% fat, 0.2% cholesterol) beginning at 6 weeks of age until they were sacrificed at 4 months. We compared the extent of atherosclerosis in the cross section area of the aortic sinus using the VerHoeffs/Van Gieson stain. Inflammatory cells (neutrophils and macrophages) in the aortic lesions were quantitated by immunohistochemistry. Results: Similar to previous published reports by us and others, we found that the mean lesion area in the aortic sinus of the Adamts13−/−/ApoE−/− mice were significantly larger (mean ± SEM: 26.6 % ± 1.9 %, P<0.01) compared with ApoE−/− mice (mean ± SEM: 20.4 % ± 1.5 %). Next, we quantitated macrophage and neutrophil infiltration into lesions in the aortic sinus by immunohistochemistry. We observed significantly increased macrophages (mac-3 positive) and neutrophils (Ly6 B.2 positive) recruitment in the aortic sinus of Adamts13−/−/ApoE−/− mice compared with ApoE−/− mice. The mean lesion area in the aortic sinus of Adamts13−/−/Vwf−/−/ApoE−/− mice (mean ± SEM: 15.2 % ± 1.5 %) were similar to Vwf−/−/ApoE−/− mice (mean ± SEM: 15.6 % ± 0.9 %), suggesting that the accelerated atherosclerosis observed in ADAMTS13-deficient mice is VWF-dependent. Finally, macrophages and neutrophils recruitment in the aortic sinus of Adamts13−/−/Vwf−/−/ApoE−/− mice were similar to Vwf−/−/ApoE−/− mice, suggesting that increased vascular inflammation observed in ADAMTS13-deficient mice is also VWF-dependent. Total cholesterol and triglyceride levels were similar among groups fed a high-fat Western diet. Conclusion: These findings reveal that VWF-deficiency abrogates accelerated early atherosclerosis in ADAMTS13-deficient mice, suggesting that VWF the only relevant substrate for ADAMTS13 in murine atherosclerosis. Disclosures: Lentz: Novo Nordisk A/S: Consultancy, Investigator Other.

WO12-OR-3 ATHEROSCLEROSIS DEVELOPMENT IN ADULT HETEROZYGOUS APOLIPOPROTEIN E-DEFICIENT MICE OFFSPRING IS DETERMINED IN UTERO BY MATERNAL GENOTYPE

2007 ◽  
Vol 8 (1) ◽  
pp. 12
Author(s):  
F.E. Alkemade ◽  
A.C. Gittenberger-de Groot ◽  
A.E. Schiel ◽  
C.J. van Munsteren ◽  
B. Hogers ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
In Utero ◽  
Maternal Genotype ◽  
Atherosclerosis Development ◽  
Deficient Mice
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