scholarly journals Inulin attenuates atherosclerosis in apolipoprotein E-deficient mice

2006 ◽  
Vol 96 (5) ◽  
pp. 840-844 ◽  
Author(s):  
Marie-Hélène Rault-Nania ◽  
Elyett Gueux ◽  
Céline Demougeot ◽  
Christian Demigné ◽  
Edmond Rock ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Atherosclerotic Lesion ◽  
Plaque Formation ◽  
Control Group ◽  
Apo E ◽  
Atherosclerotic Plaque Formation ◽  
Deficient Mice ◽  
Long Chain

Effects of different inulin-type fructan fractions were studied on atherosclerotic plaque formation in male apo E-deficient mice. Thirty-two mice were randomly divided into four groups and received either a semi-purified sucrose-based diet (control group), or diets in which sucrose was replaced in part by various inulin-type fructans (10 g/100 g): long-chain inulin, oligofructose, or an oligofructose-enriched inulin for 16 weeks. The presence of atherosclerotic plaques was assessed by histomorphometry in the aortic sinus. The apo E-deficient mice fed long-chain inulin or an oligofructose-enriched inulin had about 35 % and 25 % less atherosclerotic lesion area compared with the control group, respectively. Feeding long-chain inulin significantly reduced plasma cholesterol concentrations (P<0·001), and the three inulin-type fructans reduced triacylglycerol (TAG) concentrations compared with the control group (P<0·001). Both the long-chain inulin and an oligofructose-enriched inulin significantly lowered hepatic cholesterol concentrations compared with the control diet (P<0·05). Hepatic TAG concentrations were significantly lower in all three groups fed the fructan-supplemented diets v. the control group (P<0·0001). The results of the present study suggest that inhibition of atherosclerotic plaque formation is more potent in the presence of long-chain inulin, either alone or in combination with oligofructose (an oligofructose-enriched inulin), and that this probably is related to changes in lipid metabolism.

Deficiency in TDAG51 Decreases Atherosclerotic Lesion Development in ApoE-Deficient Mice.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3940-3940
Author(s):  
Gazi S. Hossain ◽  
Ji Zhou ◽  
Kenneth Maclean ◽  
Sarka Lhotak ◽  
Sudesh K. Sood ◽  
...  
Keyword(s):  
Cell Death ◽  
Hepatic Steatosis ◽  
Plasma Cholesterol ◽  
Control Diet ◽  
Atherosclerotic Lesion ◽  
Double Knockout ◽  
Lesion Development ◽  
Ppar Γ ◽  
Deficient Mice ◽  
Atherosclerotic Lesion Development

Abstract T-cell death associated gene 51 (TDAG51) is a pro-apoptotic gene that can be induced by endoplasmic reticulum (ER) stress agents, including homocysteine, tunicamycin, thapsigargin or dithiothreitol. Our previous studies have demonstrated that transient overexpression of TDAG51 elicited significant changes in cell morphology, decreased cell adhesion and promoted detachment-induced programmed cell death (PCD). In support of these in vitro findings, we have further shown that TDAG51 expression was increased and correlated with PCD in the atherosclerotic lesions from apolipoprotein E (apoE)-deficient mice fed hyperhomocysteinemic diets, compared to mice fed control diet. We designed the current study to investigate the effect of TDAG51 deficiency in the development and progression of atherosclerosis. To assess in vivo significance of TDAG51 on atherosclerosis, we have crossed TDAG51-deficient mice with apoE-deficient mice to obtain double knockout mice. Our findings have demonstrated that TDAG51/apoE-deficient mice have a significant decrease in atherosclerotic lesion area, compared to age- and sex-matched apoE-deficient mice. Total plasma cholesterol and triglycerides as well as lipoprotein profiles were similar in both groups. However, TDAG51/apoE-deficient mice presented with increased hepatic steatosis. Further, a significant upregulation of peroxisome proliferator-activated receptor γ (PPAR-γ), a transcription factor required for adipose tissue formation, was demonstrated in TDAG51-deficient mouse embryonic fibroblasts (MEFs), compared to control wildtype MEFs. Interestingly, earlier studies in mice have reported that overexpression of PPAR-γ decreases atherosclerotic lesion development and increases hepatic steatosis - a phenotype similar to that observed in the mouse deficient in both apoE and TDAG51. Collectively, these findings provide evidence that TDAG51 mediates atherosclerotic lesion development and hepatic steatosis through a mechanism involving PPAR-γ.

P715Deletion of fibroblast activation protein decreases experimental atherosclerotic plaque formation and vulnerability

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
S Stein ◽  
J Weber ◽  
S Nusser-Stein ◽  
J Pahla ◽  
H Zhang ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Cross Sections ◽  
Aortic Root ◽  
Fibroblast Activation Protein ◽  
Plaque Formation ◽  
Type I ◽  
Plaque Vulnerability ◽  
Fibroblast Activation ◽  
Atherosclerotic Plaque Formation ◽  
Deficient Mice

Abstract Background Fibroblast activation protein (FAP) is a serine protease that is upregulated in sites of tissue remodeling, including arthritis, tumors and atherosclerosis. We have reported that FAP degrades type I collagen in human thin-cap fibroatheromata; its expression is enhanced in advanced human plaques and induced by inflammation. However, the role of endogenous FAP in atherosclerosis remains unknown. Purpose To investigate the effects of constitutive Fap loss-of-function on atherosclerotic plaque formation and vulnerability. Methods and results Male 8-week-old Apoe−/− Fap+/+ and Apoe−/− Fap−/− mice were fed a high-cholesterol diet (1.25% chol) for 12 weeks. En face analyses of thoracoabdominal aortae using Oil Red O (ORO) revealed decreased plaques in Apoe−/− Fap−/− mice (5.7±0.5%; n=21) compared to Apoe−/− Fap+/+ mice (10.7±0.7%; n=24; p<0.0001). In parallel, ORO analyses of serial aortic root cross sections showed diminished plaques in Fap-deficient mice (18.4±3.4% vs 27.6±2.1%). As a surrogate of plaque vulnerability, fibrous cap thickness was increased in Apoe−/− Fap−/− mice (65±6 mm vs 35±3 mm; p<0.01), whereas necrotic core size, plaque macrophages (CD68) and T cells (CD3) accumulation, as well as VCAM1 expression did not differ. These changes were independent of plasma triglycerides, total and LDL-cholesterol levels. Plasma of Fap-deficient mice showed decreased FAP activity compared to Fap wildtype controls. Notably, second harmonics generation in cross sections of aortic root plaques showed that the deposition and density of fibrillar collagens was enhanced in Fap-deficient (25.5±4.4%) compared to control plaques (13.8±2.5%; p<0.05). Consistently, Fap deletion led to an accumulation of uncleaved pre-COL3A1, a proteolytic target of FAP. Conclusions Constitutive Fap deletion decreases experimental atherosclerosis and features of plaque vulnerability. Thus, inhibition of FAP expression or activity may be a promising therapeutic target in atherosclerosis. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation

scholarly journals CXCR3 Antagonist NBI-74330 Attenuates Atherosclerotic Plaque Formation in LDL Receptor–Deficient Mice

2008 ◽  
Vol 28 (2) ◽  
pp. 251-257 ◽  
Author(s):  
Eva J.A. van Wanrooij ◽  
Saskia C.A. de Jager ◽  
Thomas van Es ◽  
Paula de Vos ◽  
Helen L. Birch ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Ldl Receptor ◽  
Plaque Formation ◽  
Atherosclerotic Plaque Formation ◽  
Deficient Mice

Fibronectin Isoform Containing the Alternatively-Spliced Extra Domain A in Circulation Accelerates the Development of Atherosclerosis in Mice

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2205-2205
Author(s):  
Chintan Gandhi ◽  
Mohammad Moshahid Khan ◽  
Anil K Chauhan
Keyword(s):  
Atherosclerotic Plaque ◽  
Inflammatory Responses ◽  
Conflicts Of Interest ◽  
Atherosclerotic Lesion ◽  
Plaque Formation ◽  
Western Diet ◽  
High Fat ◽  
Aortic Sinus ◽  
Atherosclerotic Plaque Formation ◽  
Alternatively Spliced

Abstract Abstract 2205 Background and Objective: The fibronectin isoform containing the alternatively-spliced extra domain A (EDA+-FN) is normally absent from the circulation, but plasma levels of EDA+-FN can become markedly elevated in several pathological conditions including atherosclerosis. It remains unclear in humans whether these elevated levels of EDA+-FN are actively contributing to disease pathogenesis, or rather simply serving as a marker associated with vascular stress and/or injury. Several in vitro studies suggest that EDA+-FN can activate toll-like receptor 4 (TLR4), an innate immune receptor that triggers pro-inflammatory responses We hypothesize that presence of EDA+-FN in plasma promotes inflammation and accelerates atherosclerotic plaque formation. Model and Method: We generated EDA+/+/ApoE−/− mice, which contain optimized spliced sites at both splicing junctions of the EDA exon and constitutively express only EDA+-FN, and EDA−/−/ApoE−/− mice, which contain an EDA-null allele of the EDA exon and express only FN lacking EDA. ApoE−/−, EDA+/+/ApoE−/− and EDA−/−/ApoE−/− were fed a high-fat Western diet (21% fat and 0.2% cholesterol) beginning at 6 weeks until they were sacrificed at 5 months of age (i.e., 14 weeks on high-fat Western diet). We compared the extent of atherosclerosis in whole aortae, stained with Oil Red O and en face lesion area measured by morphometry, and in the cross section area of the aortic sinus using the VerHoeffs/Van Gieson stain. Results: We report that atherosclerotic plaque (% of total aorta) formation in the aorta of EDA+/+/ApoE−/− mice was increased by two-fold compared to control ApoE−/− mice (P<0.0001). Deletion of the alternatively spliced EDA domain in the ApoE−/− mice (EDA−/−/ApoE−/−) significantly reduced atherosclerotic plaque formation in the aorta (P<0.05) compared to ApoE−/− mice. Total cholesterol and triglycerides levels were similar in ApoE−/−, EDA+/+/ApoE−/− and EDA−/−/ApoE−/− mice. Similarly, atherosclerotic plaque formation was significantly increased in the aortic sinus of EDA+/+/ApoE−/− mice, intermediate in control ApoE−/− mice and reduced in EDA−/−/ApoE−/− mice (P<0.05). Additionally, we found that macrophage content, as analyzed by immunohistochemistry, was significantly elevated in the aortic root lesions of EDA+/+/ApoE−/− mice and reduced in EDA−/−/ApoE−/− mice compared to ApoE−/− mice (P<0.05). Moreover, EDA+-FN did not affect the sex-dependent regulation of atherosclerosis in ApoE−/− mice. Future experiments using EDA+/+/ApoE−/−/TLR4−/− are under progress to determine whether EDA+-FN exacerbate atherosclerosis via upregulating TLR4 signaling. Conclusions: Our findings reveal that EDA+-FN is pro-inflammatory and promotes atherosclerotic lesion formation and that monitoring plasma EDA+-FN might have prognostic value in patients at high risk for atherosclerosis. Disclosures: No relevant conflicts of interest to declare.

Abstract 18661: Regulation of Lymphatic Physiology by Connexin47

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Merlijn J Meens ◽  
Issa Kutkut ◽  
Amélie Sabine ◽  
Tatiana V Petrova ◽  
Brenda R Kwak
Keyword(s):  
Atherosclerotic Plaque ◽  
Lymphatic Drainage ◽  
Plaque Formation ◽  
Lymphatic Endothelial Cells ◽  
Lipid Levels ◽  
Plaque Development ◽  
Atherosclerotic Plaque Formation ◽  
Aortic Plaques ◽  
Old Mice ◽  
Deficient Mice

Introduction: Mutations in GJC2, which encodes connexin47 (Cx47), are associated with lymphedema. Moreover, Cx47 mRNA was recently found in human lymphatic endothelial cells (LECs). Hypothesis: Lymphatic endothelial Cx47 has a role in lymphatic physiology and pathology. Methods: Confocal microscopy and qPCRs were used to assess expression of Cx47. Lymphatic drainage was studied by subcutaneous Evans Blue injections in the footpad of 12 week-old ApoE -/- or Cx47 eGFP/eGFP ApoE -/- mice. Atherosclerosis was studied in 15 months-old ApoE -/- or Cx47 eGFP/eGFP ApoE -/- mice. Results: Cx47 was expressed in lymphangions of mesenteric collecting vessels in Cx47 eGFP/eGFP Prox1-mOrange2 mice as assessed by microscopy and its expression was confirmed by qPCR on mesentery, gut and skin mRNA of ApoE -/- but not Cx47 eGFP/eGFP ApoE -/- mice. Interestingly, lymphatic drainage was enhanced in Cx47-deficient mice (n=10/11, p<0.05). To address whether Cx47 affects chronic immuno-inflammatory pathology atherosclerotic plaque formation was studied in 15-month old male ApoE -/- and Cx47 eGFP/eGFP ApoE -/- mice on regular chow. These studies showed that Cx47-deficiency does not affect the size or composition (e.g. lipid, collagen or macrophage content) of aortic plaques in the aortic root. However, plaque development in the thoracic-abdominal aorta of 15 months-old mice tended to be larger in Cx47 eGFP/eGFP ApoE -/- mice (21±5 vs 30±4 % lipid area, n=10, p=0.08). Unexpectedly, total cholesterol (TC) and LDL, but not HDL, triglycerides or free fatty acids, were increased in serum of Cx47 eGFP/eGFP ApoE -/- mice as compared to ApoE -/- serum (TC: 472±24 vs 647±18 mg/dL, n=10, p<0.01; and LDL: 272±20 vs 443±17 mg/dL, n=10, p<0.001, respectively). Increased lymphatic drainage from plaques in Cx47 eGFP/eGFP ApoE -/- mice may, partially, compensate for increased serum TC and LDL thereby preventing exuberant atherosclerotic plaque formation despite increased serum lipid levels. Conclusions: In conclusion, Cx47 is expressed in LECs of the lymphangion and seems implicated in multiple aspects of lymphatic (patho)physiology.

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