scholarly journals Astragalus flavone ameliorates atherosclerosis and hepatic steatosis via improving lipid metabolism and inhibition of inflammation in apoE-/- mice

2020 ◽  
Author(s):  
Chuanrui Ma ◽  
Jing Zhang ◽  
Shu Yang ◽  
Yunqing Hua ◽  
Jing Su ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Endothelial Dysfunction ◽  
Therapeutic Approach ◽  
Foam Cell ◽  
Cell Formation ◽  
Astragalus Membranaceus ◽  
Foam Cell Formation ◽  
Monocyte Adhesion ◽  
Lipid Disorder

Abstract Background: Atherosclerosis is a major pathogenic factor in cardiovascular diseases during the aging process. Foam cell formation and endothelial dysfunction play a key role in the initiation and development of atherosclerosis, which are affected by lipid disorder and inflammation. Therefore, the drug for inhibition of endothelial dysfunction and the subsequent foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from Astragalus membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. Methods: In this study, we determined whether TFA could inhibit atherosclerosis; and uncovered the underlying molecular mechanisms. In vivo, apoE deficient mice were treated with TFA contained in high-fat diet for 16 weeks. After treatment, aorta, macrophage and serum samples were collected to determine atherosclerotic lesions, lipid metabolism, and expression of associated genes. Concurrently, we investigated the effect of TFA on monocyte adhesion, foam cell formation, endothelial activation, and macrophage polarization in vitro and in vivo. Results: TFA reduced atherosclerotic plaque size; and enhanced lesion stability by changing the composition of plaque. Moreover, foam cell formation and its accumulation in arterial wall were attenuated by TFA, which might be attributed to improved lipid disorder, reduced inflammation, and decreased monocyte adhesion to endothelial cells. Mechanistically, TFA reduced the expression of scavenger receptor, such as CD36 and SRA; promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced the expression of miR-33, a negative regulator of cholesterol efflux as well as positive mediator on inflammation; and concurrently reduced NFkB activity, by which de-repressed ABCA1/G1 activity and inhibited the inflammation. Conclusions: This study demonstrates that TFA can attenuate atherosclerosis via dual inactivation of miR-33 and NFkB signaling pathway and inhibition of scavenger receptors (CD36 and SRA), which suggests that TFA might be a novel therapeutic approach for inhibition of atherosclerosis.

scholarly journals Astragalus Flavone Ameliorates Atherosclerosis and Hepatic Steatosis Via Inhibiting Lipid-Disorder and Inflammation in apoE−/− Mice

2020 ◽  
Vol 11 ◽  
Author(s):  
Chuanrui Ma ◽  
Jing Zhang ◽  
Shu Yang ◽  
Yunqing Hua ◽  
Jing Su ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Therapeutic Approach ◽  
Foam Cell ◽  
Cell Formation ◽  
Atherosclerotic Lesion ◽  
Underlying Mechanism ◽  
Scavenger Receptors ◽  
Foam Cell Formation ◽  
Lipid Disorder

Atherosclerosis is a major pathogenic driver of cardiovascular diseases. Foam cell formation plays a key role in atherogenesis, which is affected by lipid disorder and inflammation. Therefore, inhibition of foam cell formation is a therapeutic approach for atherosclerosis treatment. Total flavone of Astragalus membranaceus (TFA) is extracted from A. membranaceus that has protective effect on cardiovascular disease. However, the effect of TFA on atherosclerosis and the underlying mechanism remains unknown. In this study, we determined whether TFA could inhibit atherosclerosis and uncovered the underlying mechanism. In vivo, ApoE deficient mice were treated with TFA and high-fat diet for 16 weeks. Subsequently, atherosclerotic lesions, hepatic steatosis and associated genes expression in vitro and in vivo were determined. We found that TFA reduced atherosclerotic lesion size and enhanced plaque stability, which might be attributed to improved lipid disorder, reduced inflammation and decreased monocyte adhesion. Mechanistically, TFA inhibited hepatic steatosis via regulating the genes responsible for lipid metabolism, by which ameliorating the lipid disorder. Moreover, in macrophage, TFA reduced the expression of scavenger receptors such as CD36 and SRA; and promoted the expression of ATP-binding cassette transporter A1 and G1 (ABCA1/G1). More importantly, TFA reduced miR-33 expression and dampened NFκB activity, by which de-repressing ABCA1/G1 activity and inhibiting the inflammation. Collectively, TFA can attenuate atherosclerosis via dual suppression of miR-33 and NFκB pathway, and partially through inhibition of scavenger receptors in macrophage. In addition, TFA ameliorates the hepatic steatosis and lipid disorder, which in turn contributes to the amelioration of atherosclerosis, suggesting that TFA might be a novel therapeutic approach for inhibition of atherosclerosis and hepatic steatosis.

scholarly journals Foam Cells as Therapeutic Targets in Atherosclerosis with a Focus on the Regulatory Roles of Non-Coding RNAs

2021 ◽  
Vol 22 (5) ◽  
pp. 2529
Author(s):  
Amin Javadifar ◽  
Sahar Rastgoo ◽  
Maciej Banach ◽  
Tannaz Jamialahmadi ◽  
Thomas P. Johnston ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Special Focus ◽  
Lipid Uptake ◽  
Therapeutic Goals ◽  
Expression Of Genes

Atherosclerosis is a major cause of human cardiovascular disease, which is the leading cause of mortality around the world. Various physiological and pathological processes are involved, including chronic inflammation, dysregulation of lipid metabolism, development of an environment characterized by oxidative stress and improper immune responses. Accordingly, the expansion of novel targets for the treatment of atherosclerosis is necessary. In this study, we focus on the role of foam cells in the development of atherosclerosis. The specific therapeutic goals associated with each stage in the formation of foam cells and the development of atherosclerosis will be considered. Processing and metabolism of cholesterol in the macrophage is one of the main steps in foam cell formation. Cholesterol processing involves lipid uptake, cholesterol esterification and cholesterol efflux, which ultimately leads to cholesterol equilibrium in the macrophage. Recently, many preclinical studies have appeared concerning the role of non-encoding RNAs in the formation of atherosclerotic lesions. Non-encoding RNAs, especially microRNAs, are considered regulators of lipid metabolism by affecting the expression of genes involved in the uptake (e.g., CD36 and LOX1) esterification (ACAT1) and efflux (ABCA1, ABCG1) of cholesterol. They are also able to regulate inflammatory pathways, produce cytokines and mediate foam cell apoptosis. We have reviewed important preclinical evidence of their therapeutic targeting in atherosclerosis, with a special focus on foam cell formation.

scholarly journals Structure and Dynamics of Oxidized Lipoproteins In Vivo: Roles of High-Density Lipoprotein

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Hiroyuki Itabe ◽  
Naoko Sawada ◽  
Tomohiko Makiyama ◽  
Takashi Obama
Keyword(s):  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Oxidized Lipoproteins

Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). Mounting clinical evidence has supported the involvement of oxLDL in cardiovascular diseases. High-density lipoprotein (HDL) is known as anti-atherogenic; however, recent studies have shown circulating oxidized HDL (oxHDL) is related to cardiovascular diseases. A modified structure of oxLDL, which was increased in the plasma of patients with acute myocardial infarction, was characterized. It had two unique features: (1) a fraction of oxLDL accompanied oxHDL, and (2) apoA1 was heavily modified, while modification of apoB, and the accumulation of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) was less pronounced. When LDL and HDL were present at the same time, oxidized lipoproteins actively interacted with each other, and oxPC and lysoPC were transferred to another lipoprotein particle and enzymatically metabolized rapidly. This brief review provides a novel view on the dynamics of oxLDL and oxHDL in circulation.

Metformin inhibits monocyte adhesion to endothelial cells and foam cell formation

2003 ◽  
Vol 3 (4) ◽  
pp. 302-310 ◽  
Author(s):  
Jean-Claude Mamputu ◽  
Nicolas Wiernsperger ◽  
Geneviève Renier
Keyword(s):  
Endothelial Cells ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Monocyte Adhesion

scholarly journals The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 334
Author(s):  
Ji-Eun Kim ◽  
Jin-Sun Kim ◽  
Min-Jee Jo ◽  
Eunjung Cho ◽  
Shin-Young Ahn ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Lipid Metabolism ◽  
Foam Cell ◽  
Cell Formation ◽  
Visceral Obesity ◽  
Foam Cell Formation ◽  
Acid Oxidation ◽  
Plasminogen Activator Inhibitor 1 ◽  
Fetuin A ◽  
Pai 1

Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.

Abstract 424: An IFNg-regulated Macrophage Protein Network Links Type 2 Diabetes to Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Catherine A Reardon ◽  
Amulya Lingaraju ◽  
Kelly Q Schoenfelt ◽  
Guolin Zhou ◽  
Ning-Chun Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Increased Risk ◽  
Macrophage Dysfunction ◽  
Macrophage Protein

Type 2 diabetics have a higher risk for atherosclerosis, but the mechanisms underlying the increased risk are poorly understood. Macrophages, which are activated in type 2 diabetes (T2D) and have a role in all stages of atherogenesis, are an attractive link. Our hypothesis is that T2D promotes macrophage dysfunction to promote atherosclerosis. To investigate the relationship between T2D and macrophage dysfunction, we used a proteomics approach to identify dysregulated proteins secreted from peritoneal macrophages in a diet induced mouse model of obesity and insulin resistance in the absence of hypercholesterolemia. Twenty-seven T2D responsive proteins were identified that predict defects in many of the critical functions of macrophages in atherosclerosis (e.g. decreased apoE- cholesterol efflux; decreased MFGE8 – efferocytosis, increased MMP12- matrix degradation). The macrophages from lean and obese mice were not lipid loaded, but the obese macrophages accumulated significantly more cholesterol when exposed to high levels of atherogenic lipoproteins in vitro suggesting that dysregulation of the T2D responsive proteins in diabetic mice render macrophages more susceptible to cholesterol loading. Importantly, many of these same protein changes, which were present in atherosclerotic Ldlr-/- mice with T2D, were normalized when these mice were fed non-diabetogenic hypercholesterolemic diets. Thus, foam cell formation in the presence and absence of T2D produces distinct effects on macrophage protein levels, and hence function. Further, we identify IFNγ as a mediator of the T2D responsive protein dysfunction. IFNγ, but not other cytokines, insulin or glucose, promote the T2D responsive protein dysregulation and increased susceptibility to cholesterol accumulation in vitro and the dysregulation is not observed in macrophage foam cells obtained from obese, diabetic IFNγ receptor 1 knockout animals. We also demonstrate that IFNγ can target these proteins in arterial wall macrophages in vivo . These studies suggest that IFNγ is an important mediator of macrophage dysfunction in T2D that may contribute to the enhanced cardiovascular risk in these patients.

Prednisone and Its Active Metabolite Prednisolone Attenuate Lipid Accumulation in Macrophages

2019 ◽  
Vol 25 (2) ◽  
pp. 174-186
Author(s):  
Helana Jeries ◽  
Nina Volkova ◽  
Claudia Grajeda-Iglesias ◽  
Mahmoud Najjar ◽  
Mira Rosenblat ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Accumulation ◽  
Cholesterol Metabolism ◽  
Foam Cell ◽  
Ex Vivo ◽  
Cholesterol Biosynthesis ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell ◽  
Healthy Human

Background: Synthetic forms of glucocorticoids (GCs; eg, prednisone, prednisolone) are anti-inflammatory drugs that are widely used in clinical practice. The role of GCs in cardiovascular diseases, including atherosclerosis, is highly controversial, and their impact on macrophage foam cell formation is still unknown. We investigated the effects of prednisone and prednisolone on macrophage oxidative stress and lipid metabolism. Methods and Results: C57BL/6 mice were intraperitoneally injected with prednisone or prednisolone (5 mg/kg) for 4 weeks, followed by lipid metabolism analyses in the aorta and peritoneal macrophages. We also analyzed the effect of serum samples obtained from 9 healthy human volunteers before and after oral administration of prednisone (20 mg for 5 days) on J774A.1 macrophage atherogenicity. Finally, J774A.1 macrophages, human monocyte-derived macrophages, and fibroblasts were incubated with increasing concentrations (0-200 ng/mL) of prednisone or prednisolone, followed by determination of cellular oxidative status, and triglyceride and cholesterol metabolism. Prednisone and prednisolone treatment resulted in a significant reduction in triglyceride and cholesterol accumulation in macrophages, as observed in vivo, ex vivo, and in vitro. These effects were associated with GCs’ inhibitory effect on triglyceride- and cholesterol-biosynthesis rates, through downregulation of diacylglycerol acyltransferase 1 and HMG-CoA reductase expression. Glucocorticoid-induced reduction of cellular lipid accumulation was mediated by the GC receptors on the macrophages, because the GC-receptor antagonist (RU486) abolished these effects. In fibroblasts, unlike macrophages, GCs showed no effects. Conclusion: Prednisone and prednisolone exhibit antiatherogenic activity by protecting macrophages from lipid accumulation and foam cell formation.

Effects of diosgenin and its derivatives on atherosclerosis

2019 ◽  
Vol 10 (11) ◽  
pp. 7022-7036 ◽  
Author(s):  
Fang-Chun Wu ◽  
Jian-Guo Jiang
Keyword(s):  
Endothelial Dysfunction ◽  
Lipid Profile ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Macrophage Foam Cell

The effects of diosgenin are discussed with respect to endothelial dysfunction, lipid profile, macrophage foam cell formation, VSMC viability, thrombosis and inflammation during the formation of atherosclerosis.

scholarly journals A Growth Hormone-Releasing Peptide Promotes Mitochondrial Biogenesis and a Fat Burning-Like Phenotype through Scavenger Receptor CD36 in White Adipocytes

Endocrinology ◽  
2007 ◽  
Vol 148 (3) ◽  
pp. 1009-1018 ◽  
Author(s):  
Amélie Rodrigue-Way ◽  
Annie Demers ◽  
Huy Ong ◽  
André Tremblay
Keyword(s):  
Mitochondrial Biogenesis ◽  
Foam Cell ◽  
Uncoupling Protein ◽  
Scavenger Receptor ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Ppar Γ ◽  
Cd36 Expression ◽  
White Fat

Whereas the uptake of oxidized lipoproteins by scavenger receptor CD36 in macrophages has been associated with foam cell formation and atherogenesis, little is known about the role of CD36 in regulating lipid metabolism in adipocytes. Here we report that treatment of 3T3-L1 adipocytes with hexarelin, a GH-releasing peptide that interacts with CD36, resulted in a depletion of intracellular lipid content with no significant change in CD36 expression. Microarray analysis revealed an increased pattern in several genes involved in fatty acid mobilization toward the mitochondrial oxidative phosphorylation process in response to hexarelin. Interestingly, many of these up-regulated genes are known targets of peroxisomal proliferator-activated receptor (PPAR)-γ, such as FATP, CPT-1, and F1-ATPase, suggesting that adipocyte response to hexarelin may involve PPARγ activation. Expression studies also indicate an increase in thermogenic markers PPARγ coactivator 1α and uncoupling protein-1, which are normally expressed in brown adipocytes. Electron microscopy of hexarelin-treated 3T3-L1 adipocytes showed an intense and highly organized cristae formation that spans the entire width of mitochondria, compared with untreated cells, and cytochrome c oxidase activity was enhanced by hexarelin, two features characteristic of highly oxidative tissues. A similar mitochondrial phenotype was detected in epididymal white fat of mice treated with hexarelin, along with an increased expression of thermogenic markers that was lost in treated CD36-null mice, suggesting that the ability of hexarelin to promote a brown fat-like phenotype also occurs in vivo and is dependent on CD36. These results provide a potential role for CD36 to impact the overall metabolic activity of fat usage and mitochondrial biogenesis in adipocytes.

Foam cell formation in vivo is pro-fibrotic

2015 ◽  
Vol 241 (1) ◽  
pp. e81-e82 ◽  
Author(s):  
A. Newby ◽  
A. Thomas
Keyword(s):  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation
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