Electronegative Low-Density Lipoprotein L5 Induces Adipose Tissue Inflammation Associated With Metabolic Syndrome

Ke, Liang‐Yin; Chan, Hua‐Chen; Chan, Hsiu-Chuan; Kalu, Franklin Chikodi Udo; Lee, Hsiang‐Chun; Lin, I‐Ling; Jhuo, Shih-Jie; Lai, Wen‐Ter; Tsao, Chen-Rong; Sawamura, Tatsuya; Dixon, Richard A. F.; Chen, Chu‐Huang; Chu, Chih‐Sheng; Shin, Shyi–Jang

doi:10.1210/jc.2017-01657

Cited by 16 publications

(20 citation statements)

References 38 publications

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“…The fast protein liquid chromatography analysis showed that the proportion of L5 levels was 5.3 ± 6.9% in MetS patients. The value was significantly higher than that (2.1 ± 1.4%) in healthy participants in our previous study.…”

Section: Resultscontrasting

confidence: 78%

“…Other investigators have also reported that electronegative LDL can promote triglyceride accumulation in cardiomyocytes and induce inflammasome activation in human macrophages. Recently, we reported that L5 isolated from MetS patients could induce adipose inflammation by promoting macrophage maturation and infiltration into adipose tissue. A recent study showed that chemical composition and atherogenic effects of the LDL subfractions in healthy controls and MetS patients were different.…”

Section: Introductionmentioning

confidence: 88%

“…MetS is an entity characterized with multiple risk factors for cardiovascular disease, including abdominal obesity, high‐normal or high blood glucose, triglyceride, blood pressure levels and low high‐density lipoprotein cholesterol level. Recently, we have observed that human electronegative low‐density lipoprotein (LDL; L5) is elevated in people with MetS, as well as patients with hypercholesterolemia, type 2 diabetes and acute myocardial infarction. L5 can tremendously accelerate atherosclerotic processes, such as endothelial cell apoptosis, platelet aggregation, C‐reactive protein overproduction and impairment of endothelial cell regeneration.…”

Section: Introductionmentioning

confidence: 99%

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Electronegative low‐density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade

Chen

Chan

et al. 2019

J of Diabetes Invest

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Aims/Introduction: Electronegative low-density lipoprotein (L5) is the most atherogenic fraction of low-density lipoprotein and is elevated in people with metabolic syndrome (MetS), whereas the retinol-binding protein 4 receptor (stimulated by retinoic acid 6 [STRA6]) cascade is disrupted in various organs of patients with obesity-related diseases. Our objective was to investigate whether L5 from MetS patients capably induces pathogenesis of aorta through disrupting the STRA6 cascade. Material and Methods: We examined the in vivo and in vitro effects of L5 on the STRA6 cascade and aortic atherogenic markers. To investigate the role of this cascade on atherosclerotic formation, crbp1 transfection was carried out in vitro.Results: This study shows that L5 activates atherogenic markers (p38 mitogen-activated protein kinases, pSmad2 and matrix metallopeptidase 9) and simultaneously suppresses STRA6 signals (STRA6, cellular retinol-binding protein 1, lecithin-retinol acyltransferase, retinoic acid receptor-a and retinoid X receptor-a) in aortas of L5-injected mice and L5-treated human aortic endothelial cell lines and human aortic smooth muscle cell lines. These L5-induced changes of the STRA6 cascade and atherogenic markers were reversed in aortas of LOX1 -/mice and in LOX1 ribonucleic acid-silenced human aortic endothelial cell lines and human aortic smooth muscle cell lines. Furthermore, crbp1 gene transfection reversed the disruption of the STRA6 cascade, the phosphorylation of p38 mitogen-activated protein kinases and Smad2, and the elevation of matrix metallopeptidase 9 in L5treated human aortic endothelial cell lines. Conclusions: This study shows that L5 from MetS patients induces atherogenic markers by disrupting STRA6 signaling. Suppression of STRA6 might be one novel pathogenesis of aorta in patients with MetS.

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Section: Resultscontrasting

confidence: 78%

Section: Introductionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

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Electronegative low‐density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade

Chen

Chan

et al. 2019

J of Diabetes Invest

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“…В частности, М2-макрофаги, экспрессирующие SR-I1 (CD163) и SR-E3 (CD206), могут активно секретировать ключевые антивоспалительные цитокины -IL-10 и рецепторный антагонист IL-1 [190]. В целом увеличение экспрессии SR-I1 на макрофагах способствует ограничению продукции провоспалительных цитокинов и их дифференцировки в направлении М2 [108].…”

Section: класс D представлен единственным рецептором Sr-d1 (Cd68)unclassified

“…Ожирение характеризуется активацией и увеличением числа макрофагов в жировой ткани, а при прогрессировании процесса и миграцией в жировую ткань определенного количества Т-лимфоцитов, включая рециркулирующие Th1 и Th17 иммунной памяти, а также поляризацией макрофагов в направлении М1 [216,236]. При этом провоспалительные процессы в жировой ткани дополнительно потенцируются высокими концентрациями в крови атерогенных липопротеинов [108]. Действие этих и других лигандов SR на макрофаги жировой ткани через SR-B2 (CD36) и SR-E1 (LOX-1), а также прямо на адипоциты, через CD36, способствует активации этих клеток и развитию инсулинорезистентности [27,54,182].…”

Section: Sr при развитии метаболического синдрома и диабета 2-го типаunclassified

Physiological and pathogenic role of scavenger receptors in humans

et al. 2020

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The scavenger receptors (SRs)) include > 30 different molecules structurally classified into 11 classes (A to L). They are expressed mostly on stromal macrophages, and their expression may be augmented in direct dependence with concentrations of their ligands. The SRs are heterogenous by their structure, however, being common in their functional potential. E.g., different SR classes may participate in absorption of modified low-density lipoproteins and glycated proteins, apoptotic and ageing cells, altered erythrocytes and platelets, like as a big variety of other endogenous ligands from metabolic and cellular “trash”. A common property of SRs is their participation in removal of small pathogen amounts from blood circulation, regulation of cell and tissue stress responses, ability to form complicated receptor complexes with other receptor types including integrins and toll-like receptors. Opposite to classic pattern-recognizing receptors, the SR involvement does not always elicit a pronounced cellular activation and development of pro-inflammatory cellular stress. The SR functional effects provide interactions between different physiological events and immune system, including the processes of neuroendocrine and metabolic regulation. These mechanisms provide both homeostatic stability and, likewise, act at the border of normal and pathological conditions, i.e., participating in pathogenesis of transitional processes, e.g., physiological ageing. Moreover, the SR-associated processes represent a key pathogenetic factor in different somatic diseases, e.g., those associated with low-intensity chronic inflammation, including obesity, type 2 diabetes, atherosclerosis, arterial hypertension, various neurodegenerative disorders. Similarly, the SRs are involved into the processes of cancer transformation and antitumor response, different processes of classical inflammation, from antigen presentation to the morphofunctional T cell and macrophage polarization in the inflammation foci and immunocompetent organs. SR are playing a controversial role in development of acute systemic inflammation, the main reason for lethal outcomes in the intensive care wards. Targeted effects upon the SRs represent a promising approach when treating a broad variety of diseases, whereas detection of membrane-bound and soluble SR forms could be performed by means of diagnostic and monitoring techniques in many human disorders.

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Inflammasome Activation in Human Macrophages Induced by a LDL (−) Mimetic Peptide

2019

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Electronegative Low-Density Lipoprotein L5 Induces Adipose Tissue Inflammation Associated With Metabolic Syndrome

Abstract: L5 induces adipose inflammation through LOX-1 by promoting macrophage maturation and infiltration into adipose tissue. Elevated plasma L5 levels may be a novel etiology of adipose tissue inflammation in patients with MetS.

Cited by 16 publications

References 38 publications

Electronegative low‐density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade

Electronegative low‐density lipoprotein of patients with metabolic syndrome induces pathogenesis of aorta through disruption of the stimulated by retinoic acid 6 cascade

Physiological and pathogenic role of scavenger receptors in humans

Inflammasome Activation in Human Macrophages Induced by a LDL (−) Mimetic Peptide

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