scholarly journals Dietary supplementation with Cyperus esculentus L (tiger nut) tubers attenuated atherosclerotic lesion in apolipoprotein E knockout mouse associated with inhibition of inflammatory cell responses

2005 ◽  
Vol 1 (1) ◽  
pp. 60-67 ◽  
Author(s):  
Mohamed Labib Salem ◽  
Mohsen Zommara ◽  
K. Imaizumi
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mouse ◽  
Inflammatory Cell ◽  
Atherosclerotic Lesion ◽  
Dietary Supplementation ◽  
Cyperus Esculentus ◽  
Cell Responses

Abstract 1205: Role for Nox1 NADPH Oxidase in Atherosclerosis

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Andrea L Sheehan ◽  
Maysam Takapoo ◽  
Botond Banfi ◽  
Francis J Miller
Keyword(s):  
Nadph Oxidase ◽  
Apolipoprotein E ◽  
Vascular Disease ◽  
Thoracic Aorta ◽  
Inflammatory Cell ◽  
Atherosclerotic Lesion ◽  
Atherogenic Diet ◽  
Lesion Area ◽  
Nadph Oxidases ◽  
Vascular Cell

NADPH oxidase-derived reactive oxygen species (ROS) contribute to the pathobiology of vascular disease. However, studies investigating NADPH oxidases in atherosclerosis have been limited in their ability to distinguish between the role of vascular cell and inflammatory cell -derived ROS. In this study, we examined the contribution of Nox1-derived ROS in a mouse model of atherosclerosis. Nox1 is a primary catalytic subunit of vascular cell, but not inflammatory cell, NADPH oxidase. At weaning, male apolipoprotein E deficient mice (AS, n=12) and male mice deficient in both apolipoprotein E and Nox1 (AS/Nox, n=16) received an atherogenic diet for 18 weeks. Mean blood pressures (116±3 vs. 110 ±3 mmHg; AS vs. AS/Nox, n=6), weights, and serum cholesterol levels (1578±150 vs. 1631±80 mg/dl; AS vs. AS/Nox) were similar between the AS and AS/Nox mice. As measured by lucigenin-enhanced chemiluminescence, superoxide levels were increased in segments of thoracic aorta from AS mice as compared to aorta from control mice (22±2 vs. 14±2 RLU/sec/mm 2 ; AS vs. C57BL/6; p<0.05, n=6). In contrast, superoxide levels in segments of thoracic aorta from AS/Nox mice were significantly lower (9±1 RLU/sec/mm 2 , n=6) than both AS and C57BL/6 mice. Dihydroethidium staining confirmed decreased superoxide levels in aorta of AS/Nox mice. Atherosclerotic lesion area was measured by staining the aorta en face with Oil Red O. Although atherosclerotic lesion area was reduced over the entire length of aorta in AS/Nox mice as compared to AS mice (10±1% vs. 14±1%, p<0.01), the reduction in lesion was primarily limited to the aortic arch (28±3% vs. 43±2%, p<0.001). In summary, Nox1 contributes to generation of ROS and lesion formation in atherosclerosis. These data confirm a role for vascular cell NADPH oxidases, and in particular Nox1, in vascular disease.

Deficiency of endothelial CD40 induces a stable plaque phenotype and limits inflammatory cell recruitment to atherosclerotic lesions in mice

2021 ◽  
Author(s):  
Mark Colin Gissler ◽  
Philipp Scherrer ◽  
Nathaly Anto Michel ◽  
Jan Pennig ◽  
Natalie Hoppe ◽  
...  
Keyword(s):  
Adhesion Molecule ◽  
Inflammatory Cell ◽  
Leukocyte Adhesion ◽  
Critical Role ◽  
Atherosclerotic Lesion ◽  
Intercellular Adhesion Molecule ◽  
Atherosclerotic Plaques ◽  
Chow Diet ◽  
Stable Plaque ◽  
Plaque Phenotype

Objectives: The co-stimulatory CD40L-CD40 dyad exerts a critical role in atherosclerosis by modulating leukocyte accumulation into developing atherosclerotic plaques. The requirement for cell-type specific expression of both molecules, however, remains elusive. Here, we evaluate the contribution of CD40 expressed on endothelial cells (ECs) in a mouse model of atherosclerosis. Approach & Results: Atherosclerotic plaques of Apolipoprotein E deficient (Apoe-/-) mice and humans displayed increased expression of CD40 on ECs compared to controls. To interrogate the role of CD40 on ECs in atherosclerosis, we induced EC-specific (BmxCreERT2-driven) deficiency of CD40 in Apoe-/- mice. After feeding a chow diet for 25 weeks, EC-specific deletion of CD40 (iEC-CD40) ameliorated plaque lipid deposition and lesional macrophage accumulation but increased intimal smooth muscle cell and collagen content, while atherosclerotic lesion size did not change. Leukocyte adhesion to the vessel wall was impaired in iEC-CD40-deficient mice as demonstrated by intravital microscopy. In accord, expression of vascular adhesion molecule (VCAM)-1 and intercellular adhesion molecule (ICAM)-1 in the vascular endothelium declined after deletion of CD40. In vitro, antibody-mediated inhibition of human endothelial CD40 significantly abated monocyte adhesion on ECs. Conclusions: Endothelial deficiency of CD40 in mice promotes structural features associated with a stable plaque phenotype in humans and decreases leukocyte adhesion. These results suggest that endothelial-expressed CD40 contributes to inflammatory cell migration and consecutive plaque formation in atherogenesis.

scholarly journals Androgen Receptor-Dependent and Independent Atheroprotection by Testosterone in Male Mice

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5428-5437 ◽  
Author(s):  
Johan Bourghardt ◽  
Anna S. K. Wilhelmson ◽  
Camilla Alexanderson ◽  
Karel De Gendt ◽  
Guido Verhoeven ◽  
...  
Keyword(s):  
Androgen Receptor ◽  
Apolipoprotein E ◽  
High Fat Diet ◽  
Atherosclerotic Lesion ◽  
Male Mice ◽  
Wild Type ◽  
High Fat ◽  
Lesion Area ◽  
Major Pathway

The atheroprotective effect of testosterone is thought to require aromatization of testosterone to estradiol, but no study has adequately addressed the role of the androgen receptor (AR), the major pathway for the physiological effects of testosterone. We used AR knockout (ARKO) mice on apolipoprotein E-deficient background to study the role of the AR in testosterone atheroprotection in male mice. Because ARKO mice are testosterone deficient, we sham operated or orchiectomized (Orx) the mice before puberty, and Orx mice were supplemented with placebo or a physiological testosterone dose. From 8 to 16 wk of age, the mice consumed a high-fat diet. In the aortic root, ARKO mice showed increased atherosclerotic lesion area (+80%, P &lt; 0.05). Compared with placebo, testosterone reduced lesion area both in Orx wild-type (WT) mice (by 50%, P &lt; 0.001) and ARKO mice (by 24%, P &lt; 0.05). However, lesion area was larger in testosterone-supplemented ARKO compared with testosterone-supplemented WT mice (+57%, P &lt; 0.05). In WT mice, testosterone reduced the presence of a necrotic core in the plaque (80% among placebo-treated vs. 12% among testosterone-treated mice; P &lt; 0.05), whereas there was no significant effect in ARKO mice (P = 0.20). In conclusion, ARKO mice on apolipoprotein E-deficient background display accelerated atherosclerosis. Testosterone treatment reduced atherosclerosis in both WT and ARKO mice. However, the effect on lesion area and complexity was more pronounced in WT than in ARKO mice, and lesion area was larger in ARKO mice even after testosterone supplementation. These results are consistent with an AR-dependent as well as an AR-independent component of testosterone atheroprotection in male mice.

scholarly journals Activation of the Renin-Angiotensin System Mediates the Effects of Dietary Salt Intake on Atherogenesis in the Apolipoprotein E Knockout Mouse

Hypertension ◽  
2012 ◽  
Vol 60 (1) ◽  
pp. 98-105 ◽  
Author(s):  
Chris Tikellis ◽  
Raelene J. Pickering ◽  
Despina Tsorotes ◽  
Olivier Huet ◽  
Jaye Chin-Dusting ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Knockout Mouse ◽  
Salt Intake ◽  
Renin Angiotensin System ◽  
Dietary Salt ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Dietary Salt Intake

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 &lt; 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.

scholarly journals Vitamin A-Deficient Diet Accelerated Atherogenesis in Apolipoprotein E−/−Mice and Dietaryβ-Carotene Prevents This Consequence

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Noa Zolberg Relevy ◽  
Dror Harats ◽  
Ayelet Harari ◽  
Ami Ben-Amotz ◽  
Rafael Bitzur ◽  
...  
Keyword(s):  
Vitamin A ◽  
Apolipoprotein E ◽  
Vitamin A Deficiency ◽  
Plasma Cholesterol ◽  
Atherosclerotic Lesion ◽  
Dietary Vitamin ◽  
Control Group ◽  
Chow Diet ◽  
Deficient Diet ◽  
Aortic Sinus

Vitamin A is involved in regulation of glucose concentrations, lipid metabolism, and inflammation, which are major risk factors for atherogenesis. However, the effect of vitamin A deficiency on atherogenesis has not been investigated. Therefore, the objective of the current study was to examine whether vitamin A deficiency accelerates atherogenesis in apolipoprotein E-deficient mice (apoE−/−). ApoE−/−mice were allocated into the following groups: control, fed vitamin A-containing chow diet; BC, fed chow diet fortified withDunaliellapowder containingβc isomers; VAD, fed vitamin A-deficient diet; and VAD-BC group, fed vitamin A-deficient diet fortified with aDunaliellapowder. Following 15 weeks of treatment, liver retinol concentration had decreased significantly in the VAD group to about 30% that of control group. Vitamin A-deficient diet significantly increased both plasma cholesterol concentrations and the atherosclerotic lesion area at the aortic sinus (+61%) compared to the control group. Dietaryβc fortification inhibited the elevation in plasma cholesterol and retarded atherogenesis in mice fed the vitamin A-deficient diet. The results imply that dietary vitamin A deficiency should be examined as a risk factor for atherosclerosis and that dietaryβc, as a sole source of retinoids, can compensate for vitamin A deficiency.

scholarly journals GDF11 Protects against Endothelial Injury and Reduces Atherosclerotic Lesion Formation in Apolipoprotein E-Null Mice

2016 ◽  
Vol 24 (11) ◽  
pp. 1926-1938 ◽  
Author(s):  
Wen Mei ◽  
Guangda Xiang ◽  
Yixiang Li ◽  
Huan Li ◽  
Lingwei Xiang ◽  
...  
Keyword(s):  
Apolipoprotein E ◽  
Atherosclerotic Lesion ◽  
Endothelial Injury ◽  
Lesion Formation ◽  
Atherosclerotic Lesion Formation
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