scholarly journals βCommon Receptor Mediates Erythropoietin-Conferred Protection on OxLDL-Induced Lipid Accumulation and Inflammation in Macrophages

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Tzong-Shyuan Lee ◽  
Kuo-Yun Lu ◽  
Yuan-Bin Yu ◽  
Hsueh-Te Lee ◽  
Feng-Chuan Tsai
Keyword(s):  
Lipid Accumulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Neutralizing Antibody ◽  
Foam Cells ◽  
Beneficial Effects ◽  
Inflammatory Protein ◽  
Common Receptor ◽  
Macrophage Foam Cells ◽  
Key Factor

Erythropoietin (EPO), the key factor for erythropoiesis, also protects macrophage foam cells from lipid accumulation, yet the definitive mechanisms are not fully understood.βcommon receptor (βCR) plays a crucial role in the nonhematopoietic effects of EPO. In the current study, we investigated the role ofβCR in EPO-mediated protection in macrophages against oxidized low-density lipoprotein- (oxLDL-) induced deregulation of lipid metabolism and inflammation. Here, we show thatβCR expression was mainly in foamy macrophages of atherosclerotic aortas from apolipoprotein E-deficient mice. Results of confocal microscopy and immunoprecipitation analyses revealed thatβCR was colocalized and interacted with EPO receptor (EPOR) in macrophages. Inhibition ofβCR activation by neutralizing antibody or small interfering RNA (siRNA) abolished the EPO-conferred protection in oxLDL-induced lipid accumulation. Furthermore, EPO-promoted cholesterol efflux and upregulation of ATP-binding cassette (ABC) transporters ABCA1 and ABCG1 were prevented by pretreatment withβCR neutralizing antibody orβCR siRNA. Additionally, blockage ofβCR abrogated the EPO-conferred anti-inflammatory action on oxLDL-induced production of macrophage inflammatory protein-2. Collectively, our findings suggest thatβCR may play an important role in the beneficial effects of EPO against oxLDL-elicited dysfunction of macrophage foam cells.

scholarly journals Signaling Pathways and Key Genes Involved in Regulation of foam Cell Formation in Atherosclerosis

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 584 ◽  
Author(s):  
Anastasia V. Poznyak ◽  
Wei-Kai Wu ◽  
Alexandra A. Melnichenko ◽  
Reinhard Wetzker ◽  
Vasily Sukhorukov ◽  
...  
Keyword(s):  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Foam Cell Formation ◽  
Beneficial Effects ◽  
Complex Process ◽  
Experimental Therapies ◽  
Inflammatory Drugs

Atherosclerosis is associated with acute cardiovascular conditions, such as ischemic heart disease, myocardial infarction, and stroke, and is the leading cause of morbidity and mortality worldwide. Our understanding of atherosclerosis and the processes triggering its initiation is constantly improving, and, during the last few decades, many pathological processes related to this disease have been investigated in detail. For example, atherosclerosis has been considered to be a chronic inflammation triggered by the injury of the arterial wall. However, recent works showed that atherogenesis is a more complex process involving not only the immune system, but also resident cells of the vessel wall, genetic factors, altered hemodynamics, and changes in lipid metabolism. In this review, we focus on foam cells that are crucial for atherosclerosis lesion formation. It has been demonstrated that the formation of foam cells is induced by modified low-density lipoprotein (LDL). The beneficial effects of the majority of therapeutic strategies with generalized action, such as the use of anti-inflammatory drugs or antioxidants, were not confirmed by clinical studies. However, the experimental therapies targeting certain stages of atherosclerosis, among which are lipid accumulation, were shown to be more effective. This emphasizes the relevance of future detailed investigation of atherogenesis and the importance of new therapies development.

scholarly journals The Administration of Probiotics against Hypercholesterolemia: A Systematic Review

2021 ◽  
Vol 11 (15) ◽  
pp. 6913
Author(s):  
Bhagavathi Sundaram Sivamaruthi ◽  
Muruganantham Bharathi ◽  
Periyanaina Kesika ◽  
Natarajan Suganthy ◽  
Chaiyavat Chaiyasut
Keyword(s):  
Cholesterol Biosynthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Probiotic Strain ◽  
Blood Cholesterol ◽  
Health Concern ◽  
Dietary Interventions ◽  
Cvd Risk ◽  
Beneficial Effects ◽  
Key Factor

Hypercholesterolemia is a key factor in the progression of atherosclerosis and cardiovascular disease (CVD). CVD is a significant public health concern with a high death rate. Some of the main factors linked to CVD include genetics and lifestyle. Dyslipidemia has been one of the factors related to the onset of several CVD-related diseases. Several clinicopathological studies have shown a correlation between high cholesterol levels, particularly low-density lipoprotein cholesterol (LDL-c), and CVD development. Probiotics have received a lot of attention for various beneficial effects, especially their ability to reduce blood cholesterol in humans. Probiotics were shown in several investigations to affect hypercholesterolemia by influencing cholesterol biosynthesis. The current review focuses on the human dietary interventions with probiotics and their effects on CVD risk factors and hypercholesterolemia. The outcomes are debatable and consider various parameters such as probiotic strain, dosing frequency, therapeutic response, dietary changes, and so forth. As a result, probiotics have the propensity to become dietary supplements in moderate/severe hypercholesterolemic patients, which significantly reduces the CVD risk.

scholarly journals Overexpression of low-density lipoprotein receptor and lipid accumulation in intestinal polyps in Min mice

2009 ◽  
Vol 125 (11) ◽  
pp. 2505-2510 ◽  
Author(s):  
Michihiro Mutoh ◽  
Masami Komiya ◽  
Naoya Teraoka ◽  
Toshiya Ueno ◽  
Mami Takahashi ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Intestinal Polyps ◽  
Density Lipoprotein Receptor

scholarly journals Accumulation of quercetin conjugates in blood plasma after the short-term ingestion of onion by women

2000 ◽  
Vol 279 (2) ◽  
pp. R461-R467 ◽  
Author(s):  
Jae-Hak Moon ◽  
Ritsuko Nakata ◽  
Syunji Oshima ◽  
Takahiro Inakuma ◽  
Junji Terao
Keyword(s):  
Blood Plasma ◽  
Low Density Lipoprotein ◽  
Copper Ion ◽  
Density Lipoprotein ◽  
Tocopherol Content ◽  
Human Blood Plasma ◽  
Short Term ◽  
Beneficial Effects ◽  
Human Volunteers ◽  
Conjugated Metabolites

Quercetin is a typical flavonoid present mostly as glycosides in plant foods; it has attracted much attention for its potential beneficial effects in disease prevention. In this study, we examined human volunteers after the short-term ingestion of onion, a vegetable rich in quercetin glucosides. The subjects were served diets containing onion slices (quercetin equivalent: 67.6–93.6 mg/day) with meals for 1 wk. Quercetin was only found in glucuronidase-sulfatase-treated plasma, and its concentration after 10 h of fasting increased from 0.04 ± 0.04 μM before the trial to 0.63 ± 0.72 μM after the 1-wk trial. The quercetin content in low-density lipoprotein (LDL) after glucuronidase-sulfatase treatment corresponded to <1% of the α-tocopherol content. Human LDL isolated from the plasma after the trial showed little improvement of its resistance to copper ion-induced oxidation. It is therefore concluded that conjugated metabolites of quercetin accumulate exclusively in human blood plasma in the concentration range of 10−7 ∼ 10−6 M after the short-term ingestion of vegetables rich in quercetin glucosides, although these metabolites are hardly incorporated into plasma LDL.

scholarly journals Sagunja-Tang Improves Lipid Related Disease in a Postmenopausal Rat Model and HepG2 Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Hiroe Go ◽  
Jin Ah Ryuk ◽  
Hye Won Lee ◽  
In Sil Park ◽  
Ki-Jung Kil ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Cholesterol Synthesis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Protein Levels ◽  
Related Disease

The present study was conducted to investigate the effect of Sagunja-tang on the lipid related disease in a rat model of menopausal hyperlipidemia and lipid accumulation in methyl-β-cyclodextrin-induced HepG2 cells. Inin vivostudy using menopausal hyperlipidemia rats, Sagunja-tang reduced retroperitoneal and perirenal fat, serum lipids, atherogenic index, cardiac risk factor, media thickness, and nonalcoholic steatohepatitis score, when compared to menopausal hyperlipidemia control rats. In HepG2 cells, Sagunja-tang significantly decreased the lipid accumulation, total cholesterol levels, and low-density/very-low-density lipoprotein levels. Moreover, Sagunja-tang reversed the methyl-β-cyclodextrin-induced decrease in the protein levels of critical molecule involved in cholesterol synthesis, sterol regulatory element binding protein-2, and low-density lipoprotein receptor and inhibited protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase as well as activity. Phosphorylation level of AMP-activated protein kinase was stimulated by Sagunja-tang. These results suggest that Sagunja-tang has effect on inhibiting hepatic lipid accumulation through regulation of cholesterol synthesis and AMPK activityin vitro. These observations support the idea that Sagunja-tang is bioavailable bothin vivoandin vitroand could be developed as a preventive and therapeutic agent of hyperlipidemia in postmenopausal females.

Abstract 5: Lipid Droplet Associated Hydrolase: A New Player in Cholesterol Mobilization From Foam Cells

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Younghwa Goo ◽  
Pradip Saha ◽  
Larry Chan ◽  
Antoni Paul
Keyword(s):  
Lipid Droplet ◽  
Cholesterol Efflux ◽  
Bone Marrow Cells ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Foam Cells ◽  
Peritoneal Macrophages ◽  
Cholesterol Homeostasis

Lipid laden macrophages/foam cells are a hallmark of atherosclerotic lesions from early to late stages of development. Macrophages take-up modified low-density lipoprotein (mLDL) particles and store surplus mLDL-derived cholesterol as cholesterol ester (CE) in cytoplasmic lipid droplets (LDs). Accelerating CE hydrolysis from the LDs is a plausible strategy to promote reverse cholesterol transport from the atheroma. However, the identity of the CE hydrolases that function on LDs remains unknown. Previously we identified lipid droplet-associated hydrolase (LDAH) in LDs purified from macrophages and reported that in vitro LDAH regulates CE levels by increasing CE hydrolysis. To determine the relevance of LDAH in atherogenesis, we have generated LDAH knockout (LDAH-/-) mice. Mouse peritoneal macrophages (MPM) isolated from LDAH-/- mice had increased cytoplasmic LDs, increased net CE content, and decreased cholesterol efflux. In atherosclerosis studies, both male and female LDAH-/- mice crossed with apolipoprotein E knockout (apoE-/-) mice fed a Western diet developed larger lesions. Lesions of LDAH-/-/ apoE-/- mice were characterized by increased areas of macrophages containing enlarged cytoplasms with large LDs. Supporting a direct atheroprotective role of LDAH in macrophages, lesions of apoE-/- mice that received bone marrows from LDAH-/-/apoE-/- mice progressed faster than those that received bone marrow cells from LDAH+/+/apoE-/- mice. In qPCR analyses of genes involved in cholesterol homeostasis in macrophages, we found that ABC binding cassette transporters ABCA1 and ABCG1, which mediate cholesterol efflux through the plasma membrane, were consistently decreased in LDAH-/- MPM. Further in vivo gene expression studies on macrophages selectively obtained from lesions using laser capture microdissection are underway. In conclusion, our study suggests that LDAH promotes LD CE hydrolysis and cholesterol efflux from foam cells within the atheroma, and uncovers a potential target to promote reverse cholesterol from arteries as a means of ameliorating atherosclerosis development.

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