scholarly journals miR-155 acts as an anti-inflammatory factor in atherosclerosis-associated foam cell formation by repressing calcium-regulated heat stable protein 1

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Xiaoyi Li ◽  
Deyong Kong ◽  
Heming Chen ◽  
Shuiyi Liu ◽  
Hui Hu ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Inflammatory Factor ◽  
Heat Stable ◽  
Heat Stable Protein ◽  
Anti Inflammatory

scholarly journals eIF6 Promotes Inflammatory Macrophage Phenotype, Foam Cell Formation and Atherosclerosise

2021 ◽  
Author(s):  
Junnian Zheng ◽  
Renjin Chen ◽  
Xuemei Xian ◽  
xiaoqiang Zhan ◽  
Jiajia Chang ◽  
...  
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Western Diet ◽  
Initiation Factor ◽  
Immunofluorescent Staining ◽  
Foam Cell Formation ◽  
Macrophage Phenotype ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage ◽  
Novel Therapeutic

Abstract Background：Atherosclerosis is a chronic inflammatory disease, caused by accumulation of lipid-laden and inflammatory macrophages in the artery wall. Understanding its molecular mechanisms and developing novel therapeutic targets to promote atherosclerotic regression is an important clinical goal.Methods : ApoE-/- and eIF6+/-/ApoE-/- mice were fed Western diet (WD) for 16 weeks. Molecular biology technology were performed to analyze the differences between them.Results: The mechanism by which Eukaryotic initiation factor 6 (eIF6) affects macrophages and atherosclerosis remains to be elucidated. Western blotting and real-time polymerase chain reaction (PCR ) analysis indicated significantly higher expression levels of eIF6 than those in the control in RAW264.7 cells induced by Lipopolysaccharide (LPS) and Interleukin-4 (IL4). We constructed eIF6+/-/ApoE-/- mice, the hematoxylin (HE) and Oil Red O staining analysis indicated that these mice showed a significant decrease in atherosclerotic lesion formation increased anti-inflammatory cell content in aortas, and reduced necrotic core content compared with ApoE-/- mice on a western diet for 16 weeks. eIF6 deficiency suppressed foam cell formation and promoted the anti-inflammatory macrophage phenotype in primary macrophages. More anti-inflammatory populations were observed in blood and atherosclerotic aortas of eIF6+/- ApoE-/- mice by flow cytometry. Immunofluorescent staining analysis obtained the same results.Conclusions: eIF6 deficiency protects against atherosclerosis by promoting the anti-inflammatory macrophage phenotype and reducing macrophage uptake of low-density lipoprotein (LDL), indicating that new insight into eIF6 may reveal a potential novel therapeutic target for the resolution of inflammation in atherosclerosis.

scholarly journals Role of adipokine zinc-α2-glycoprotein in coronary heart disease

2019 ◽  
Vol 317 (6) ◽  
pp. E1055-E1062
Author(s):  
Dandan Huang ◽  
Xiaoxiang Mao ◽  
Jiangtong Peng ◽  
Min Cheng ◽  
Tao Bai ◽  
...  
Keyword(s):  
Coronary Heart Disease ◽  
Heart Disease ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Atherosclerotic Plaques ◽  
293 Cells ◽  
Anti Inflammatory

Zinc-α2-glycoprotein (AZGP1) is a newly identified adipokine that is associated with lipid metabolism and vascular fibrosis. Although adipokines contribute to lipid dysfunction and its related diseases, including stroke and coronary heart disease (CHD), the role of AZGP1 remains unclear. In this study, the role of AZGP1 in atherosclerosis and CHD was investigated. Serum AZGP1 levels from control ( n = 84) and CHD ( n = 91) patients were examined by ELISA and its relationship with various clinical parameters was analyzed. Immunohistochemistry and immunofluorescence were used to detect the expression of AZGP1 and its receptor in coronary atherosclerotic arteries. THP-1 and human embryonic kidney 293 cells were used to verify its anti-inflammatory role in atherosclerosis. Serum AZGP1 levels in CHD patients were lower than controls ( P < 0.01) and independently associated with CHD prevalence ( P = 0.021). AZGP1 levels also inversely correlated with the Gensini score. Immunohistochemistry and immunofluorescence showed that AZGP1 and its receptor β3-adrenoceptor (β3-AR) colocalized in lipid-rich areas of atherosclerotic plaques, particularly around macrophages. In vitro, AZGP1 had no effect on foam cell formation but showed anti-inflammatory effects through its regulation of JNK/AP-1 signaling. In summary, AZGP1 is an anti-inflammatory agent that can be targeted for CHD treatment.

Abstract 239: Deficiency of Macrophage Epsins Impedes Atherosclerosis by Inhibiting LRP-1 Internalization and Degradation

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Megan L Brophy ◽  
Ashiqur Rahman ◽  
Yunzhou Dong ◽  
Hao Wu ◽  
Kandice L Tessneer ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Gene Profiling ◽  
Foam Cell Formation ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

Background: Atherosclerosis is caused by the chronic activation of the vascular endothelium and immune and inflammatory cell infiltration of the vascular wall, leading to enhanced inflammation and lipid accumulation. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Epsins are a family of ubiquitin-binding endocytic adaptors. However, their role in vascular inflammation is poorly understood. Our goal is to define the novel role of epsins in regulating atherogenesis. Methods and Results: We engineered mice with specific deletion of epsins in myeloid cells (MΦ-DKO). Strikingly, MΦ-DKO mice on an ApoE-/- background fed western diet exhibited reduced atherosclerotic lesion and foam cell accumulation, and diminished recruitment of immune or inflammatory cells to aortas by FACS analysis. In primary macrophages, epsin deficiency impaired foam cell formation by Oil Red O staining, and suppressed the pro-inflammatory M1 macrophage phenotype but increased the anti-inflammatory macrophage phenotype by gene profiling. Epsin deficiency did not alter levels of LDL scavenger receptors, or reverse cholesterol transport proteins, but did increase total and surface levels of LRP-1, a protein with anti-inflammatory and anti-atherosclerotic properties. Mechanistically, Epsin interacts with LRP-1 via epsin’s UIM domain. LPS treatment increased LRP-1 ubiquitination and subsequent binding to epsin, suggesting that epsin promotes the ubiquitin-dependent internalization and degradation of LRP-1. Accordingly, macrophages isolated from MΦ-DKO mice on LRP-1 heterozygous background restored the pro-inflammatory phenotype. Conclusions: Epsins promote atherogenesis by facilitating pro-inflammatory macrophage recruitment and potentiating foam cell formation by downregulating LRP-1 implicating that targeting the epsin-LRP-1 interaction may serve as a novel therapeutic strategy to treat atheromas.

scholarly journals Effects of lycopene on the induction of foam cell formation by modified LDL

2007 ◽  
Vol 293 (6) ◽  
pp. E1820-E1827 ◽  
Author(s):  
Mariarosaria Napolitano ◽  
Clara De Pascale ◽  
Caroline Wheeler-Jones ◽  
Kathleen M. Botham ◽  
Elena Bravo
Keyword(s):  
Foam Cell ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Lipid Synthesis ◽  
Receptor Activity ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Modified Ldl ◽  
Tnf Α ◽  
Anti Inflammatory

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with lycopene in the presence or absence of native LDL (nLDL) or LDL modified by oxidation (oxLDL), aggregation (aggLDL), or acetylation (acLDL). The cholesterol content, lipid synthesis, scavenger receptor activity, and the secretion of inflammatory [interleukin (IL)-1β and tumor necrosis factor (TNF)-α] and anti-inflammatory (IL-10) cytokines was determined. Lycopene was found to decrease the synthesis of cholesterol ester in incubations without LDL or with oxLDL while triacylglycerol synthesis was reduced in the presence of oxLDL and aggLDL. Scavenger receptor activity as assessed by the uptake of acLDL was decreased by ∼30% by lycopene. In addition, lycopene inhibited IL-10 secretion by up to 74% regardless of the presence of nLDL or aggLDL but did not affect IL-1β or TNF-α release. Lycopene also reduced the relative abundance of mRNA transcripts for scavenger receptor A (SR-A) in THP-1 macrophages treated with aggLDL. These findings suggest that lycopene may reduce macrophage foam cell formation induced by modified LDL by decreasing lipid synthesis and downregulating the activity and expression of SR-A. However, these effects are accompanied by impaired secretion of the anti-inflammatory cytokine IL-10, suggesting that lycopene may also exert a concomitant proinflammatory effect.

scholarly journals Mechanistic Insight into PPARγ and Tregs in Atherosclerotic Immune Inflammation

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhao Gao ◽  
Xinrui Xu ◽  
Yang Li ◽  
Kehan Sun ◽  
Manfang Yang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Foam Cell ◽  
Cell Formation ◽  
Autoimmune Response ◽  
Inflammatory Factors ◽  
Foam Cell Formation ◽  
Inflammatory Factor ◽  
Acid Uptake ◽  
Endothelial Cell Function ◽  
Immune Mediated

Atherosclerosis (AS) is the main pathological cause of acute cardiovascular and cerebrovascular diseases, such as acute myocardial infarction and cerebral apoplexy. As an immune-mediated inflammatory disease, the pathogenesis of AS involves endothelial cell dysfunction, lipid accumulation, foam cell formation, vascular smooth muscle cell (VSMC) migration, and inflammatory factor infiltration. The nuclear receptor peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in lipid metabolism, inflammation, and apoptosis by antagonizing the Wnt/β-catenin pathway and regulating cholesterol efflux and inflammatory factors. Importantly, PPARγ-dependant fatty acid uptake is critical for metabolic programming. Activated PPARγ can exert an anti-atherosclerotic effect by inhibiting the expression of various inflammatory factors, improving endothelial cell function, and restraining the proliferation and migration of VSMCs. Regulatory T cells (Tregs) are the only subset of T lymphocytes that have a completely negative regulatory effect on the autoimmune response. They play a critical role in suppressing excessive immune responses and inflammatory reactions and widely affect AS-associated foam cell formation, plaque rupture, and other processes. Recent studies have shown that PPARγ activation promotes the recruitment of Tregs to reduce inflammation, thereby exerting its anti-atherosclerotic effect. In this review, we provide an overview of the anti-AS roles of PPARγ and Tregs by discussing their pathological mechanisms from the perspective of AS and immune-mediated inflammation, with a focus on basic research and clinical trials of their efficacies alone or in combination in inhibiting atherosclerotic inflammation. Additionally, we explore new ideas for AS treatment and plaque stabilization and establish a foundation for the development of natural PPARγ agonists with Treg recruitment capability.

scholarly journals Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Chunping Liu ◽  
Guiling Chen ◽  
Yanfen Chen ◽  
Yue Dang ◽  
Guangning Nie ◽  
...  
Keyword(s):  
Foam Cell ◽  
Heart Function ◽  
Cell Formation ◽  
Small Animal ◽  
Raw264.7 Cells ◽  
Foam Cell Formation ◽  
Inflammatory Factor ◽  
Lipid Deposition ◽  
Vascular Stenosis

Atherosclerosis (AS) is a type of chronic vascular disease, and its etiology is not yet fully understood. AS is characterized by lipid deposition, atherosclerotic plaque formation, vascular stenosis or even complete blockage of the blood vessel wall. Clinical studies have shown that Danlou tablets (DLTs) can improve the heart function, quality of life, and prognosis of patients with coronary heart disease and myocardial infarction. However, its mechanism of action remains unknown. Our study revealed that DLTs ameliorated ApoE−/−AS mouse aortic atherosclerotic plaques [hematoxylin-eosin (HE) staining and small animal ultrasound] and reduced CD68+ macrophage infiltration, the expression of the inflammatory factor interferon-gamma (IFN-γ), vascular smooth muscle α-actin, and serum lipid levels. In vitro, in the macrophage foaming model, DLTs partially restored the activity of RAW264.7 cells, reduced the uptake of lipid droplets, and inhibited lipid droplet accumulation and apoptosis within BMDMs. We also found that Torin1, an autophagy agonist, reduced intracellular lipid deposition in BMDMs, as did DLTs. Moreover, DLTs upregulated the expression of the autophagy-related protein LC3II and decreased p62 accumulation in RAW264.7 cells. DLTs also inhibited the phosphorylation of p-PI3K, p-Akt, and p-mTOR, leading to upregulated autophagy in RAW264.7 cells. In summary, our results suggested that DLTs can promote autophagy in macrophages by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing foam cell formation and improving atherosclerosis.

Abstract 94: Deficiency of Epsins in Macrophages Ameliorates Atherosclerosis by Attenuating Inflammation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Megan L Brophy ◽  
Yunzhou Dong ◽  
Hao Wu ◽  
Kai Song ◽  
Ashiqur Rahman ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Inflammatory Cell ◽  
Foam Cell ◽  
Oxidized Ldl ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Phenotype ◽  
M1 Macrophage ◽  
Anti Inflammatory ◽  
Inflammatory Macrophage

Background: Atherosclerosis is caused by the immune and inflammatory cell infiltration of the vascular wall, leading to enhanced inflammation and lipid accumulation. Understanding the molecular mechanisms underlying this disease is critical for the development of new therapies. Our recently studies demonstrate that endothelial epsins, a family of ubiquitin-binding endocytic adaptors are critical regulators of atherosclerosis. However, whether epsins in macrophages play a role in regulating vascular inflammation is unknown. We hypothesize that epsins in macrophages promote inflammation to facilitate atherogenesis. Methods and Results: We engineered myeloid cell-specific epsins double knockout mice (MΦ-DKO) on an ApoE-/- background fed western diet. Strikingly, these mice exhibited reduced atherosclerotic lesion formation, diminished immune and inflammatory cell recruitment to aortas and reduced cleaved caspase 3 staining but increased α-SMA staining within aortic root sections. Epsin deficiency hindered foam cell formation, suppressed the pro-inflammatory M1 macrophage phenotype but increased the anti-inflammatory macrophage phenotype, and enhanced efferocytosis in primary macrophages. Mechanistically, we show that epsin loss specifically increases total and surface levels of LRP-1, a protein with anti-inflammatory properties without altering levels of LDL scavenger receptors. We further show that epsin and LRP-1 interact via epsin’s UIM domain. Oxidized LDL treatment increased LRP-1 ubiquitination and subsequent binding to epsin while mutation of cytoplasmic lysine residues attenuated LRP-1 ubiquitination, suggesting that epsin promotes the ubiquitin-dependent internalization and degradation of LRP-1. Importantly, MΦ-DKO/ApoE null mice on LRP-1 heterozygous background restored atherosclerosis, suggesting that epsin-mediated LRP-1 downregulation in macrophages plays a pivotal role in propelling atherogenesis. Conclusions: Macrophage epsins promote atherogenesis, in part, by facilitating pro-inflammatory macrophage recruitment and potentiating foam cell formation by downregulating LRP-1, implicating that targeting epsin in macrophages may serve as a novel therapeutic strategy to treat atheroma.

Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages

2018 ◽  
Vol 46 (01) ◽  
pp. 87-106 ◽  
Author(s):  
Hung-Chih Lin ◽  
Chong-Kuei Lii ◽  
Hui-Chun Chen ◽  
Ai-Hsuan Lin ◽  
Ya-Chen Yang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Cholesterol Accumulation ◽  
Macrophage Foam Cell ◽  
Macrophage Foam Cells ◽  
Mrna And Protein Expression ◽  
Anti Inflammatory

oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent atherosclerosis.

Abstract 404: Induction of MiR133a Expression By IL-19 Targets LDLRAP1 and Reduces Oxidized LDL Uptake in VSMC

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Khatuna Gabunia ◽  
Allison Herman ◽  
Mitali Ray ◽  
Sheri Kelemen ◽  
Ross England ◽  
...  
Keyword(s):  
Foam Cell ◽  
Inflammatory Diseases ◽  
Oxidized Ldl ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Adaptor Protein ◽  
Foam Cell Formation ◽  
Anti Inflammatory

Introduction: The transformation of vascular smooth muscle cells (VSMC) into foam cells leading to increased plaque size and decreased stability is a key, yet understudied step in atherogenesis. We reported that Interleukin-19 (IL-19), a novel, anti-inflammatory cytokine, attenuates atherosclerosis by anti-inflammatory effects on VSMC. We tested the hypothesis that one mechanism was reduction in VSMC foam cell formation. Methods and Results: In this work we report that IL-19 induces expression of miR133a, a muscle-specific miRNA, in VSMC. Although previously unreported, we show that miR133a can target and reduce mRNA abundance, mRNA stability, and protein expression of Low Density Lipoprotein Receptor Adaptor Protein 1, (LDLRAP1), an adaptor protein which functions to internalize the LDL receptor. Mutations in this gene lead to LDL receptor malfunction and cause the Autosomal Recessive Hypercholesterolemia (ARH) disorder in humans. We also show that IL-19 reduces lipid accumulation in VSMC, as well as LDLRAP1 expression and oxLDL uptake in a miR133a-dependent mechanism. We show that LDLRAP1 is expressed in plaque and neointimal VSMC of mouse and human injured arteries. Transfection of miR133a and LDLRAP1 siRNA into VSMC reduces their proliferation and uptake of oxLDL. miR133a is significantly increased in plasma from hyperlipidemic compared with normolipidemic patients. Summary and conclusions: miR133a targets LDLRAP1 3’UTR and reduces its expression. Expression of miR133a in IL-19 stimulated VSMC represents a previously unrecognized link between vascular lipid metabolism and inflammation, and may represent a therapeutic opportunity to combat vascular inflammatory diseases.

EM of human atherosclerosis: Aortic fatty streaks with transitional lesion features

1992 ◽  
Vol 50 (1) ◽  
pp. 622-623
Author(s):  
K. Florian Klemp ◽  
J.R. Guyton
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Processing Technique ◽  
Foam Cell Formation ◽  
Tissue Preparation ◽  
Electron Microscopic ◽  
Extracellular Lipid ◽  
Electron Microscopic Cytochemistry ◽  
Human Atherosclerosis ◽  
Clinically Significant

The earliest distinctive lesions in human atherosclerosis are fatty streaks (FS), characterized initially by lipid-laden foam cell formation. Fibrous plaques (FP), the clinically significant lesions, differ from FS in several respects. In addition to foam cells, the FP also exhibit fibromuscular proliferation and a necrotic core region rich in extracellular lipid. The possible transition of FS into mature FP has long been debated, however. A subset of FS described by Katz etal., was intermediate in lipid composition between ordinary FS and FP. We investigated this hypothesis by electron microscopic cytochemistry by employing a tissue processing technique previously described by our laboratory. Osmium-tannic acid-paraphenylenediamine (OTAP) tissue preparation enabled ultrastructural analysis of lipid deposits to discern features characteristic of mature fibrous plaques.

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