scholarly journals The G2A Receptor Deficiency Aggravates Atherosclerosis in Rats by Regulating Macrophages and Lipid Metabolism

2021 ◽  
Vol 12 ◽  
Author(s):  
Xueqin Cui ◽  
Roumei Xing ◽  
Yue Tian ◽  
Man Wang ◽  
Yue Sun ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Akt Pathway ◽  
Atherosclerotic Plaques ◽  
Potential Therapeutic Target ◽  
Lipid Disorder ◽  
Atherosclerosis Development ◽  
G Protein Coupled ◽  
Macrophage Accumulation ◽  
Single Knockout

The orphan G protein-coupled receptor G2A has been linked to atherosclerosis development. However, available data from mouse models are controversial. Rat G2A receptor bears more similarities with its human homolog. We proposed that the atherosclerosis model established from Ldlr–/– rat, which has been reported to share more similar phenotypes with the human disease, may help to further understand this lipid receptor. G2A deletion was found markedly aggravated in the lipid disorder in the rat model, which has not been reported in mouse studies. Examination of aortas revealed exacerbated atherosclerotic plaques in G2A deficient rats, together with increased oxidative stress and macrophage accumulation. In addition, consistently promoted migration and apoptosis were noticed in G2A deficient macrophages, even in macrophages from G2A single knockout rats. Further analysis found significantly declined phosphorylation of PI3 kinase (PI3K) and AKT, together with reduced downstream genes Bcl2 and Bcl-xl, suggesting possible involvement of PI3K/AKT pathway in G2A regulation to macrophage apoptosis. These data indicate that G2A modulates atherosclerosis by regulating lipid metabolism and macrophage migration and apoptosis. Our study provides a new understanding of the role of G2A in atherosclerosis, supporting it as a potential therapeutic target.

scholarly journals Atypical Chemokine Receptors in Cardiovascular Disease

2019 ◽  
Vol 119 (04) ◽  
pp. 534-541 ◽  
Author(s):  
Selin Gencer ◽  
Emiel van der Vorst ◽  
Maria Aslani ◽  
Christian Weber ◽  
Yvonne Döring ◽  
...  
Keyword(s):  
G Protein ◽  
Chemokine Receptors ◽  
Cellular Response ◽  
Current Knowledge ◽  
G Protein Coupled Receptors ◽  
Signalling Pathways ◽  
Atherosclerosis Development ◽  
G Protein Coupled ◽  
Precise Role

AbstractInflammation has been well recognized as one of the main drivers of atherosclerosis development and therefore cardiovascular diseases (CVDs). It has been shown that several chemokines, small 8 to 12 kDa cytokines with chemotactic properties, play a crucial role in the pathophysiology of atherosclerosis. Chemokines classically mediate their effects by binding to G-protein-coupled receptors called chemokine receptors. In addition, chemokines can also bind to atypical chemokine receptors (ACKRs). ACKRs fail to induce G-protein-dependent signalling pathways and thus subsequent cellular response, but instead are able to internalize, scavenge or transport chemokines. In this review, we will give an overview of the current knowledge about the involvement of ACKR1–4 in CVDs and especially in atherosclerosis development. In the recent years, several studies have highlighted the importance of ACKRs in CVDs, although there are still several controversies and unexplored aspects that have to be further elucidated. A better understanding of the precise role of these atypical receptors may pave the way towards novel and improved therapeutic strategies.

scholarly journals Lipid Metabolism in Macrophages: Focus on Atherosclerosis

Biomedicines ◽  
2020 ◽  
Vol 8 (8) ◽  
pp. 262
Author(s):  
Vasily N. Sukhorukov ◽  
Victoria A. Khotina ◽  
Yegor S. Chegodaev ◽  
Ekaterina Ivanova ◽  
Igor A. Sobenin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Atherosclerotic Plaques ◽  
Lipid Uptake ◽  
Therapeutic Approaches ◽  
Cellular Functions ◽  
Intracellular Lipid ◽  
New Therapeutic Approaches ◽  
Intracellular Lipid Accumulation ◽  
Atherosclerosis Development ◽  
The Moment

Mechanisms of lipid homeostasis and its impairment are of crucial importance for atherogenesis, and their understanding is necessary for successful development of new therapeutic approaches. In the arterial wall, macrophages play a prominent role in intracellular lipid accumulation, giving rise to foam cells that populate growing atherosclerotic plaques. Under normal conditions, macrophages are able to process substantial amounts of lipids and cholesterol without critical overload of the catabolic processes. However, in atherosclerosis, these pathways become inefficient, leading to imbalance in cholesterol and lipid metabolism and disruption of cellular functions. In this review, we summarize the existing knowledge on the involvement of macrophage lipid metabolism in atherosclerosis development, including both the results of recent studies and classical concepts, and provide a detailed description of these processes from the moment of lipid uptake with lipoproteins to cholesterol efflux.

scholarly journals Gentiopicroside Ameliorates Glucose and Lipid Metabolism in T2DM by Activating PI3K/AKT Pathway Via FGFR1

2021 ◽  
Author(s):  
Zhanchi Xu ◽  
Zeyuan Lin ◽  
Jingran Zeng ◽  
Rui Chen ◽  
Chuting Li ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Glucose Metabolism ◽  
Hepg2 Cells ◽  
Growth Factor Receptor ◽  
Akt Pathway ◽  
Phosphatidylinositol 3 Kinase ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders

Abstract Background: Abnormalities in lipid and glucose metabolism are are constantly occured in type 2 diabetes (T2DM). However, it can be ameliorated by gentiopicroside (GPS). Considering the key role of fibroblast growth factor receptor 1/phosphatidylinositol 3-kinase/protein kinase B (FGFR1/PI3K/AKT) pathway in T2DM, we explore the possible mechanism of GPS on lipid and glucose metabolism through its effects on FGFR1/PI3K/AKT pathway.Methods: Palmitic acid (PA)-induced HepG2 cells and a db/db mice were used to clarify the role and mechanism of polydatin on lipid and glucose metabolism.Results: GPS ameliorated glucose and lipid metabolism disorders in db/db mice and PA-induced HepG2 cells. Furthermore, GPS activated FGFR1/PI3K/AKT pathway including increased the protein expression of FGFR1 and promoted the phosphorylation of PI3K, AKT and FoxO1. Additionally, knockdown of FGFR1 reversed the activation of PI3K/AKT pathway by GPS.Conclusions: The present study demontrates that GPS ameliorates glucose and lipid metabolism disorders via activation of FGFR1/PI3K/AKT pathway.

scholarly journals The Role of the VEGF Family in Atherosclerosis Development and Its Potential as Treatment Targets

2022 ◽  
Vol 23 (2) ◽  
pp. 931
Author(s):  
Siarhei A. Dabravolski ◽  
Victoria A. Khotina ◽  
Andrey V. Omelchenko ◽  
Vladislav A. Kalmykov ◽  
Alexander N. Orekhov
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Lipid Metabolism ◽  
Cardiovascular Diseases ◽  
Growth Factor ◽  
Vascular Endothelial ◽  
Treatment Targets ◽  
Atherosclerosis Development ◽  
Endothelial Growth Factor ◽  
General Regulation

The vascular endothelial growth factor (VEGF) family, the crucial regulator of angiogenesis, lymphangiogenesis, lipid metabolism and inflammation, is involved in the development of atherosclerosis and further CVDs (cardiovascular diseases). This review discusses the general regulation and functions of VEGFs, their role in lipid metabolism and atherosclerosis development and progression. These functions present the great potential of applying the VEGF family as a target in the treatment of atherosclerosis and related CVDs. In addition, we discuss several modern anti-atherosclerosis VEGFs-targeted experimental procedures, drugs and natural compounds, which could significantly improve the efficiency of atherosclerosis and related CVDs’ treatment.

Abstract 412: Apelin-13 Enhances Atherosclerotic Plaque Stability in Apoe-Deficient Mice

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Rodrigo A Fraga-Silva ◽  
Hugo Seeman ◽  
Fabrizio Montecucco ◽  
Analina R da Silva ◽  
Fabienne Burger ◽  
...  
Keyword(s):  
Shear Stress ◽  
Atherosclerotic Plaque ◽  
Experimental Period ◽  
Serum Levels ◽  
Lesion Size ◽  
Plaque Formation ◽  
Atherosclerotic Plaques ◽  
Plaque Stability ◽  
Atherosclerosis Development

Introduction: Atherosclerosis remains one of the main cause of death worldwide and substantial efforts have been made to identify novel approaches to improve the management of this disorder. Apelin is an endogenous peptidergic family with essential role on the cardiovascular hemostasis and pathologies. Recent studies pointed out a fundamental contribution of Apelin system on atherosclerosis development; however, such reports revealed contradictory data, and to date, it is difficult to accurately define the beneficial or deleterious role of Apelin in atherosclerosis. Objective: To better understand the role of Apelin system on atherosclerosis, we aimed to investigate the actions of Apelin-13 treatment on atherosclerotic plaques composition, focusing on features of plaque vulnerability. Methods: Apolipoprotein E gene-deleted mice (n=40) were fed with western-type diet for 11 weeks. Atherosclerotic plaque formation was induced in the carotid artery by a shear stress modifier device, which exposed the vessel to distinct patterns of shear stress, resulting in plaque formation with different composition. The mice were treated with Apelin-13 (2 mg/Kg/day) or vehicle for the last 3 weeks of experimental period. Results: Apelin-13 treatment did not change atherosclerotic plaque size in the aorta, neither altered the lipid content of low shear stress and oscillatory shear stress-induced plaques in the carotid. However, Apelin-13 remarkably ameliorated plaque stability by increasing intraplaque collagen content, which was associated with a reduction of MMP-9 expression. Furthermore, Apelin decreased cell infiltration (neutrophil and macrophage) and intraplaque reactive oxygen species content. Interestingly, Apelin-13 treatment reduced total cholesterol, LDL levels and free fatty acids serum levels, while HDL, triglycerides serum levels were not significantly changed. Conclusion: Apelin-13 treatment for 3 weeks did not alter the lesion size, but significantly enhances the stable phenotype of atherosclerotic plaques and improved serum lipid profile. These results indicate that activation of Apelin system enhances plaque stability.

scholarly journals Central orexin (hypocretin) 2 receptor antagonism reduces ethanol self-administration, but not cue-conditioned ethanol-seeking, in ethanol-preferring rats

2013 ◽  
Vol 16 (9) ◽  
pp. 2067-2079 ◽  
Author(s):  
Robyn Mary Brown ◽  
Shaun Yon-Seng Khoo ◽  
Andrew John Lawrence
Keyword(s):  
Nucleus Accumbens ◽  
G Protein Coupled Receptors ◽  
Self Administration ◽  
Potential Therapeutic Target ◽  
Guide Cannulae ◽  
Hypothalamic Neuropeptides ◽  
Reinforcing Effects ◽  
G Protein Coupled ◽  
The Brain

Abstract Orexins are hypothalamic neuropeptides which bind to two G-protein-coupled receptors, orexin-1 (OX1R) and orexin-2 (OX2R) receptor. While a role for OX1R has been established in both ethanol reinforcement and ethanol-seeking behaviour, the role of OX2R in these behaviours is relatively less-studied. The aim of this study was to determine the role of central OX2R in ethanol-taking and ethanol-seeking behaviour. Indiana ethanol-preferring rats were trained to self-administer ethanol (10% w/v) or sucrose (0.7–1% w/v) in the presence of reward-associated cues before being implanted with indwelling guide cannulae. The selective OX2R antagonist TCS-OX2-29 was administered i.c.v. to assess its effect on operant self-administration and cue-induced reinstatement following extinction. Following i.c.v. injection TCS-OX2-29 reduced self-administration of ethanol, but not sucrose. Despite reducing ethanol self-administration, TCS-OX2-29 had no impact on cue-induced reinstatement of ethanol seeking. To determine where in the brain OX2R were acting to modulate ethanol self-administration, TCS-OX2-29 was microinjected into either the shell or core of the nucleus accumbens (NAc). Intra-NAc core, but not shell, infusions of TCS-OX2-29 decreased responding for ethanol. Importantly, the doses of TCS-OX2-029 used were non-sedating. Collectively, these findings implicate OX2R in the NAc in mediating the reinforcing effects of ethanol. This effect appears to be drug-specific as antagonism of central OX2R had no impact on sucrose self-administration. Thus, OX2R in addition to OX1R may represent a potential therapeutic target for the treatment of ethanol-use disorders. However, unlike OX1R, no impact of OX2R antagonism was observed on cue-induced reinstatement, suggesting a more prominent role for OX2R in ethanol self-administration compared to cue-conditioned ethanol-seeking.

A Cytochemical Study of Glucose-6-Phosphatase (G-6-PASE) in Cells Participating in Atherogenesis of Rabbit Aorta

1975 ◽  
Vol 33 ◽  
pp. 460-461
Author(s):  
Sidney D. Kobernick ◽  
Edna A. Elfont ◽  
Neddra L. Brooks
Keyword(s):  
Lipid Metabolism ◽  
New Zealand ◽  
Aortic Wall ◽  
Rabbit Aorta ◽  
Plaque Formation ◽  
Metabolic Changes ◽  
Atherosclerotic Plaques ◽  
Cytochemical Study ◽  
Cellular Alteration ◽  
New Zealand White Rabbits

This cytochemical study was designed to investigate early metabolic changes in the aortic wall that might lead to or accompany development of atherosclerotic plaques in rabbits. The hypothesis that the primary cellular alteration leading to plaque formation might be due to changes in either carbohydrate or lipid metabolism led to histochemical studies that showed elevation of G-6-Pase in atherosclerotic plaques of rabbit aorta. This observation initiated the present investigation to determine how early in plaque formation and in which cells this change could be observed.Male New Zealand white rabbits of approximately 2000 kg consumed normal diets or diets containing 0.25 or 1.0 gm of cholesterol per day for 10, 50 and 90 days. Aortas were injected jin situ with glutaraldehyde fixative and dissected out. The plaques were identified, isolated, minced and fixed for not more than 10 minutes. Incubation and postfixation proceeded as described by Leskes and co-workers.

Glucose disposal and lipid metabolism in man: role of thyroid hormones

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S130-S131
Author(s):  
M. J. MÜLLER ◽  
A. G. BURGER ◽  
E. JEQUIER ◽  
K.J. ACHESON
Keyword(s):  
Lipid Metabolism ◽  
Thyroid Hormones ◽  
Glucose Disposal

Genetic background of cholesterol absorption efficacy. The role of Niemann–Pick C1-like 1 receptor and its genetic variation in lipid metabolism

2010 ◽  
Vol 151 (34) ◽  
pp. 1376-1383 ◽  
Author(s):  
Mariann Harangi ◽  
István Balogh ◽  
János Harangi ◽  
György Paragh
Keyword(s):  
Genetic Variation ◽  
Lipid Metabolism ◽  
Genetic Background ◽  
Cholesterol Absorption ◽  
Niemann Pick

A Niemann–Pick C1-like-1 egy szterolfelismerő domént tartalmazó membránfehérje, amelyet nagy számban expresszálnak csúcsi felszínükön a bélhámsejtek. Az utóbbi évek vizsgálatai azt igazolták, hogy ez a fehérje szükséges a szabad koleszterin bejutásához a bélhámsejtekbe a bél lumenéből. Biokémiai vizsgálatok azt igazolták, hogy a Niemann–Pick C1-like-1-hez kötődik az ezetimib, amely egy hatékony koleszterinfelszívódást gátló szer. A bélből történő koleszterinfelszívódás ütemében és az ezetimibkezelés hatékonyságában tapasztalt egyéni eltérések hátterében felmerült néhány Niemann–Pick C1-like-1 génvariáció oki szerepe.

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