Krill Oil Combined with Bifidobacterium animalis subsp. lactis F1-7 Alleviates the Atherosclerosis of ApoE−/− Mice

There has been an increasing number of studies on the interaction between active substances and probiotics to improve disease. Both krill oil (KO) and probiotics have the effect of improving atherosclerotic cardiovascular disease, but the combined effect has not been explored. Therefore, the purpose of this study was to explore the improvement effect of KO combined with probiotics on atherosclerosis. The atherosclerotic plaque area of ApoE−/− mice was detected after the intervention of KO, Bifidobacterium animalis subsp. lactis F1-7 (Bif. animalis F1-7), and KO combined with Bif. animalis F1-7. The results showed that Bif. animalis F1-7, KO, and KO combined with Bif. animalis F1-7 could significantly reduce the area of atherosclerotic plaque and improve the levels of serum lipids and inflammatory factors. They could regulate the farnesoid X receptor (FXR)/cholesterol 7-alpha hydroxylase (CYP7A1) pathway to reduce lipid accumulation. The intervention groups could also improve the inflammatory response by downregulating the Toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88) pathway. The anti-inflammatory effect of the interaction group was significantly better than that of KO. It proved that Bif. animalis F1-7 might play a synergistic effect in the improvement of inflammation by KO to the alleviation of atherosclerosis.

Download Full-text

Atherosclerotic plaque area by transesophageal echocardiography (TEE) related to coronary artery disease (CAD) and risk factors

Atherosclerosis ◽

10.1016/s0021-9150(00)80119-7 ◽

2000 ◽

Vol 151 (1) ◽

pp. 27

Author(s):

M Kinoshita ◽

Y Iwama ◽

A Sugo ◽

S Ohashi ◽

H Sato ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Transesophageal Echocardiography ◽

Atherosclerotic Plaque ◽

Plaque Area ◽

Artery Disease

Download Full-text

Abstract 102: Cd98 Modulates Atherosclerotic Plaque Morphology by Regulating Smooth Muscle Cell Proliferation via the P-38 Map Kinase Pathway

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvb.35.suppl_1.102 ◽

2015 ◽

Vol 35 (suppl_1) ◽

Author(s):

Sara McCurdy ◽

Yvonne Baumer ◽

Franz Hess ◽

William A Boisvert

Keyword(s):

Cell Proliferation ◽

Smooth Muscle ◽

Smooth Muscle Cells ◽

Smooth Muscle Cell ◽

Atherosclerotic Plaque ◽

Necrotic Core ◽

Plaque Morphology ◽

Fibrous Cap ◽

Plaque Area

Smooth muscle cells (SMC) are known to migrate and proliferate to form a stabilizing fibrous cap that encapsulates atherosclerotic plaques. It has been shown that CD98hc, a transmembrane protein with a known role in amino acid transport and integrin signaling, is involved in proliferation and survival of various cell types including SMC. Based on these data, we hypothesized that CD98hc deficiency selectively in SMC would have pathogenic effects on atherosclerosis development and plaque composition. To test this, we utilized mice with SMC-specific deletion of the CD98hc ( CD98hc fl/fl SM22Cre + ) to determine the effects of CD98hc deficiency on SMC function in the context of atherosclerosis. We performed in vitro proliferation and survival/apoptosis assays to investigate the role of CD98hc in the proliferation and survival of primary mouse aortic vascular smooth muscle cells. We found that VSMC isolated from whole aortas of CD98hc -/- animals displayed approximately 60% reduced cell counts compared to control (41 ± 8.2% of control) after 5 days in culture. EdU assays in vivo showed a defect in the ability of CD98hc -/- SMC to proliferate, with 25% reduction in EdU-positive VSMC compared to controls (2.3 ± 0.2% vs 3 ± 0.2%). In addition, caspase-3 staining of SMC in vitro displayed a 41% increase in propensity of CD98hc -/- SMC to undergo apoptosis compared to controls (7.9 ± 0.6% vs 5.6 ± 0.5%). Furthermore, the absence of CD98hc in SMC caused a sharp increase in phosphorylated p-38, which was partially abrogated towards control levels when the cells were treated with PDGF-BB to induce proliferation. Long-term atherosclerosis study using SMC-CD98hc -/- /LDLR -/- mice showed that atherosclerotic plaque morphology was altered with increased necrotic core area (25.8 ± 1.9% vs 10.9 ± 1.6% necrotic core area per plaque area) due to a reduction in infiltration of SMC within the plaque (2.1 ± 0.4% vs 4.3 ± 0.4% SM22α positive area per plaque area) compared to control LDLR -/- mice. These data support an important role for CD98hc and its regulation of p-38 MAP kinase signaling in aortic vascular smooth muscle cell proliferation and survival. We conclude that CD98hc is critical for the formation of fibrous cap that is important in maintaining the stability of atherosclerotic plaque.

Download Full-text

Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88

Innate Immunity ◽

10.1177/1753425920927479 ◽

2020 ◽

pp. 175342592092747

Author(s):

Yajie Yang ◽

Yan Hu ◽

Yile Zhou ◽

Tao Liang ◽

Haihong Tang ◽

...

Keyword(s):

Inflammatory Factors ◽

Myeloid Differentiation ◽

Study Group ◽

Tlr4 Expression ◽

Wild Type ◽

Human Embryonic Kidney ◽

Gram Negative ◽

Tnf Α ◽

Polymorphic Variants ◽

Myeloid Differentiation Factor

TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.

Download Full-text

Aryl Hydrocarbon Receptor Modulates the Expression of TNF-α and IL-8 in Human Sebocytes via the MyD88-p65NF-κB/p38MAPK Signaling Pathways

Journal of Innate Immunity ◽

10.1159/000491029 ◽

2018 ◽

Vol 11 (1) ◽

pp. 41-51 ◽

Cited By ~ 6

Author(s):

Xiao-Xiao Hou ◽

Guangjie Chen ◽

Amir M. Hossini ◽

Tingting Hu ◽

Lanqi Wang ◽

...

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Physiological Stress ◽

Acne Vulgaris ◽

Receptor Protein ◽

Inflammatory Factors ◽

Induced Expression ◽

Aryl Hydrocarbon ◽

Tnf Α ◽

P38mapk Signaling ◽

Myeloid Differentiation Factor

Activation of Toll-like receptor (TLR)-2 and subsequent inflammatory response contribute to lesion development in acne vulgaris. A cross-talk between aryl hydrocarbon receptor (AhR), a cytosolic receptor protein that responds to environmental and physiological stress, and TLRs has recently been reported. In this study, we explored the possible role of AhR in the effects induced on cultured human SZ95 sebocytes by peptidoglycan (PGN), a classic TLR2 agonist. PGN-induced secretion of inflammatory factors TNF-α and IL-8 in human SZ95 sebocytes was suppressed after knockdown of AhR and pretreatment with the AhR antagonist CH223191. In addition, the AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) enhanced TNF-α and IL-8 secretion in PGN-pretreated sebocytes. Furthermore, PGN-induced expression of myeloid differentiation factor 88 (MyD88), phospho-p38MAPK (p-p38MAPK), and p-p65NF-κB was strengthened by TCDD and repressed by CH223191. AhR inhibition by transfecting shRNA blocked the ability of PGN to stimulate phosphorylation of p38MAPK and p65NF-κB in SZ95 sebocytes. Overall, these data demonstrate that AhR is able to modulate PGN-induced expression of TNF-α and IL-8 in human SZ95 sebocytes involving the MyD88-p65NF-κB/p38MAPK signaling pathway, which probably indicates a new mechanism in TLR2-mediated acne.

Download Full-text

LncRNA kcnq1ot1 promotes lipid accumulation and accelerates atherosclerosis via functioning as a ceRNA through the miR-452-3p/HDAC3/ABCA1 axis

Cell Death and Disease ◽

10.1038/s41419-020-03263-6 ◽

2020 ◽

Vol 11 (12) ◽

Author(s):

Xiao-Hua Yu ◽

Wen-Yi Deng ◽

Jiao-Jiao Chen ◽

Xiao-Dan Xu ◽

Xian-Xia Liu ◽

...

Keyword(s):

Cardiovascular Disease ◽

Atherosclerotic Plaque ◽

Lipid Accumulation ◽

Cholesterol Efflux ◽

Underlying Mechanism ◽

Western Diet ◽

Plaque Area ◽

Abca1 Expression ◽

Potential Contributor ◽

Mouse Aorta

AbstractKcnq1 overlapping transcript 1 (kcnq1ot1), an imprinted antisense lncRNA in the kcnq1 locus, acts as a potential contributor to cardiovascular disease, but its role in atherosclerosis remains unknown. The aim of this study was to explore the effects of kcnq1ot1 on atherogenesis and the underlying mechanism. Our results showed that kcnq1ot1 expression was significantly increased in mouse aorta with atherosclerosis and lipid-loaded macrophages. Lentivirus-mediated kcnq1ot1 overexpression markedly increased atherosclerotic plaque area and decreased plasma HDL-C levels and RCT efficiency in apoE−/− mice fed a Western diet. Upregulation of kcnq1ot1 also reduced the expression of miR-452-3p and ABCA1 but increased HDAC3 levels in mouse aorta and THP-1 macrophages. Accordingly, kcnq1ot1 overexpression inhibited cholesterol efflux and promoted lipid accumulation in THP-1 macrophages. In contrast, kcnq1ot1 knockdown protected against atherosclerosis in apoE−/− mice and suppressed lipid accumulation in THP-1 macrophages. Mechanistically, kcnq1ot1 enhanced HDAC3 expression by competitively binding to miR-452-3p, thereby inhibiting ABCA1 expression and subsequent cholesterol efflux. Taken together, these findings suggest that kcnq1ot1 promotes macrophage lipid accumulation and accelerates the development of atherosclerosis through the miR-452-3p/HDAC3/ABCA1 pathway.

Download Full-text

Metoprolol Reduces Proinflammatory Cytokines and Atherosclerosis in ApoE−/−Mice

BioMed Research International ◽

10.1155/2014/548783 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 4

Author(s):

Marcus A. Ulleryd ◽

Evelina Bernberg ◽

Li Jin Yang ◽

Göran M. L. Bergström ◽

Maria E. Johansson

Keyword(s):

Total Cholesterol ◽

Thoracic Aorta ◽

Atherosclerotic Plaque ◽

Proinflammatory Cytokines ◽

Serum Levels ◽

Adrenoceptor Antagonist ◽

Plaque Area ◽

Cholesterol Levels ◽

Antiatherosclerotic Effect ◽

Inflammatory Effect

A few studies in animals and humans suggest that metoprolol (β1-selective adrenoceptor antagonist) may have a direct antiatherosclerotic effect. However, the mechanism behind this protective effect has not been established. The aim of the present study was to evaluate the effect of metoprolol on development of atherosclerosis in ApoE−/−mice and investigate its effect on the release of proinflammatory cytokines. Male ApoE−/−mice were treated with metoprolol (2.5 mg/kg/h) or saline for 11 weeks via osmotic minipumps. Atherosclerosis was assessed in thoracic aorta and aortic root. Total cholesterol levels and Th1/Th2 cytokines were analyzed in serum and macrophage content in lesions by immunohistochemistry. Metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta (P<0.05versus Control). Further, metoprolol reduced serum TNFαand the chemokine CXCL1 (P<0.01versus Control for both) as well as decreasing the macrophage content in the plaques (P<0.01versus Control). Total cholesterol levels were not affected. In this study we found that a moderate dose of metoprolol significantly reduced atherosclerotic plaque area in thoracic aorta of ApoE−/−mice. Metoprolol also decreased serum levels of proinflammatory cytokines TNFαand CXCL1 and macrophage content in the plaques, showing that metoprolol has an anti-inflammatory effect.

Download Full-text

Virtual Transcriptomics

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.315969 ◽

2021 ◽

Author(s):

Andrew J. Buckler ◽

Eva Karlöf ◽

Mariette Lengquist ◽

T. Christian Gasser ◽

Lars Maegdefessel ◽

...

Keyword(s):

Gene Expression ◽

Myocardial Infarction ◽

Computed Tomography ◽

Ischemic Stroke ◽

Atherosclerotic Plaque ◽

Computed Tomography Angiography ◽

Machine Intelligence ◽

Diagnostic Methods ◽

Plaque Morphology ◽

Atherosclerotic Cardiovascular Disease

Objective: Therapeutic advancements in atherosclerotic cardiovascular disease have improved prevention of ischemic stroke and myocardial infarction, but diagnostic methods for atherosclerotic plaque phenotyping to aid individualized therapy are lacking. In this feasibility study, we aimed to elucidate plaque biology by decoding the molecular phenotype of plaques through analysis of computed-tomography angiography images, making a predictive model for plaque biology referred to as virtual transcriptomics. Approach and Results: We employed machine intelligence using paired computed-tomography angiography and transcriptomics from carotid endarterectomies of 40 patients undergoing stroke-preventive surgery for carotid stenosis. Computed tomography angiographies were analyzed with novel software for accurate characterization of plaque morphology and plaque transcriptomes obtained from microarrays, followed by mathematical modeling for prediction of molecular signatures. Four hundred fourteen coding and noncoding RNAs were robustly predicted using supervised models to estimate gene expression based on plaque morphology. Examples of predicted transcripts included ion transporters, cytokine receptors, and a number of microRNAs whereas pathway analyses demonstrated enrichment of several biological processes relevant for the pathophysiology of atherosclerosis and plaque instability. Finally, the ability of the models to predict plaque gene expression was demonstrated using computed tomography angiographies from 4 sequestered patients and comparisons with transcriptomes of corresponding lesions. Conclusions: The results of this pilot study show that atherosclerotic plaque phenotyping by image analysis of conventional computed-tomography angiography can elucidate the molecular signature of atherosclerotic lesions in a multiscale setting. The study holds promise for optimized personalized therapy in the prevention of myocardial infarction and ischemic stroke, which warrants further investigations in larger cohorts.

Download Full-text

Atherosclerotic plaque characterization using plaque area variation in IVUS images during compression: a computational investigation

Revista Brasileira de Engenharia Biomédica ◽

10.1590/rbeb.2014.013 ◽

2014 ◽

Vol 30 (2) ◽

pp. 159-172 ◽

Cited By ~ 1

Author(s):

Matheus Cardoso Moraes ◽

Fernando Mitsuyama Cardoso ◽

Sérgio Shiguemi Furuie

Keyword(s):

Atherosclerotic Plaque ◽

Plaque Characterization ◽

Computational Investigation ◽

Plaque Area ◽

Area Variation

Download Full-text

Contrast-enhanced ultrasonography for assessing neovascularization of carotid atherosclerotic plaque

Bulletin of Russian State Medical University ◽

10.24075/brsmu.2019.057 ◽

2019 ◽

pp. 24-31

Author(s):

A.N. Evdokimenko ◽

A.O. Chechetkin ◽

L.D. Druina ◽

M.M. Tanashyan

Keyword(s):

Atherosclerotic Plaque ◽

Quantitative Methods ◽

Analysis Data ◽

Carotid Atherosclerotic Plaque ◽

Visual Scale ◽

Plaque Area ◽

Contrast Enhanced ◽

Increased Risk ◽

Contrast Enhanced Ultrasonography

Neovascularization of a carotid atherosclerotic plaque (AP) is associated with an increased risk of stroke. Contrast-enhanced ultrasonography (CEUS) is a widely used method for imaging intraplaque neovascularization in vivo. Unfortunately, there are no standardized guidelines for CEUS interpretation. The aim of this study was to identify the most reliable method for CEUS-based assessment of AP neovascularization. Seventy-eight AP were removed during carotid endarterectomy in 73 patients, of whom 5 had AP on both sides, and examined morphologically. All patients underwent preoperative duplex scanning and CEUS; Sonovue was used as a contrast agent. AP neovascularization was assessed on a 4-grade visual scale and with 3 different quantitative methods using QLAB software. On the visual scale (method 1), poorly (37%) and moderately (51%) vascularized plaques were the most common. Quantitative analysis (data were presented as Me (Q1; Q3)) revealed that the number of blood vessels per 1 cm2 of the plaque (method 2) was 16 (10; 26), the ratio of the total vessel area to the plaque area (method 3) was 6% (3; 9), and AP ROI (method 4) was 2.6 dB (1.8; 4.1). Significant correlations were demonstrated between the results produced by method 2 and method 3 (р < 0.0001), method 3 and method 2 (p = 0.0006), and between pathomorphological findings and the results produced by methods 1–3, especially method 2 (p < 0.004). AP ROI brightness did not correlate with other results. The presence of hyperechoic components (calcifications) in AP dramatically reduced the reliability of US-based intraplaque neovascularization assessment. The most accurate CEUS-based quantitative method for assessing intraplaque neovascularization is estimation of blood vessel number per 1 cm2 of the plaque.

Download Full-text