Journal ArticleDOI
Xanthine Oxidase Induces Foam Cell Formation through LOX-1 and NLRP3 Activation
TLDR
Xanthine oxidase induces foam cell formation in large part through activation of LOX-1 - NLRP3 pathway in both VSMCs and THP-1 cells, but uric acid-induced foam cells formation is exclusively through CD36 pathway.Abstract:
Xanthine oxidase catalyzes the oxidation of xanthine to uric acid. This process generates excessive reactive oxygen species (ROS) that play an important role in atherogenesis. Recent studies show that LRR and PYD domains-containing protein 3 (NLRP3), a component of the inflammasome, may be involved in the formation of foam cells, a hallmark of atherosclerosis. This study was designed to study the role of various scavenger receptors and NLRP3 inflammasome in xanthine oxidase and uric acid-induced foam cell formation. Human vascular smooth muscle cells (VSMCs) and THP-1 macrophages were treated with xanthine oxidase or uric acid. Xanthine oxidase treatment (of both VSMCs and THP-1 cells) resulted in foam cell formation in concert with generation of ROS and expression of cluster of differentiation 36 (CD36) and oxidized low density lipoprotein (lectin-like) receptor 1 (LOX-1), but not of scavenger receptor A (SRA). Uric acid treatment resulted in foam cell formation, ROS generation and expression of CD36, but not of LOX-1 or SRA. Further, treatment of cells with xanthine oxidase, but not uric acid, activated NLRP3 and its downstream pro-inflammatory signals- caspase-1, interleukin (IL)-1β and IL-18. Blockade of LOX-1 or NLRP3 inflammasome with specific siRNAs reduced xanthine oxidase-induced foam cell formation, ROS generation and activation of NLRP3 and downstream signals. Xanthine oxidase induces foam cell formation in large part through activation of LOX-1 - NLRP3 pathway in both VSMCs and THP-1 cells, but uric acid-induced foam cell formation is exclusively through CD36 pathway. Further, LOX-1 activation is upstream of NLRP3 activation.read more
Citations
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Journal ArticleDOI
Oxidative Stress in Atherosclerosis.
TL;DR: The role of ROS and anti-oxidant mechanisms in the development and progression of atherosclerosis, the role of oxidized low-density lipoprotein cholesterol, and potential anti-Oxidant therapeutic strategies relevant to Atherosclerosis are discussed.
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Metabolomics for Investigating Physiological and Pathophysiological Processes
TL;DR: How metabolomics is yielding important new insights into a number of important biological and physiological processes is explored, with a major focus on illustrating how metabolomics and discoveries made through metabolomics are improving the understanding of both normal physiology and the pathophysiology of many diseases.
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Targeting Early Atherosclerosis: A Focus on Oxidative Stress and Inflammation
Patricia Marchio,Sol Guerra-Ojeda,José M. Vila,Martin Aldasoro,Victor M. Victor,María Dolores Mauricio +5 more
TL;DR: Inflammation and immunity are key factors for the development and complications of atherosclerosis, and therefore, the whole atherosclerotic process is a target for diagnosis and treatment.
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Cardiovascular risk in inflammatory arthritis: rheumatoid arthritis and gout
Romy Hansildaar,Daisy Vedder,Milad Baniaamam,Anne Kathrin Tausche,Martijn Gerritsen,Michael T Nurmohamed +5 more
TL;DR: Clinical guidelines and implementation of cardiovascular risk management in daily clinical practice, as well as unmet needs and areas for further investigation, will be discussed.
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Oxidative Stress and Antioxidants in Atherosclerosis Development and Treatment.
Anastasia V. Poznyak,Andrey V. Grechko,Varvara A. Orekhova,Yegor S Chegodaev,Wei-Kai Wu,Alexander N. Orekhov +5 more
TL;DR: The current knowledge on oxidative stress in atherosclerosis and potential antioxidant approaches is summarized and several important antioxidant molecules of plant origin that appear to be promising for treatment of Atherosclerosis are discussed.
References
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Journal ArticleDOI
NLRP3 inflammasomes are required for atherogenesis and activated by cholesterol crystals
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Journal ArticleDOI
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Peter Duewell,Hajime Kono,Katey J. Rayner,Cherilyn M. Sirois,Gregory I. Vladimer,Franz Bauernfeind,George S. Abela,Luigi Franchi,Gabriel Núñez,Max Schnurr,Terje Espevik,Egil Lien,Katherine A. Fitzgerald,Kenneth L. Rock,Kathryn J. Moore,Samuel D. Wright,Veit Hornung,Eicke Latz +17 more
TL;DR: This corrects the article to show that the method used to derive the H2O2 “spatially aggregating force” is a two-step process, not a single step, like in the previous version of this paper.
Journal ArticleDOI
Lectin-like, oxidized low-density lipoprotein receptor-1 (LOX-1) : A critical player in the development of atherosclerosis and related disorders
Jawahar L. Mehta,Jiawei Chen,Paul L. Hermonat,Francesco Romeo,Francesco Romeo,Giuseppe Novelli,Giuseppe Novelli +6 more
TL;DR: Recent studies show upregulation of LOX-1 in the ischemic-reperfused myocardium, and this receptor may be a novel, exciting target for drug therapy.
Journal ArticleDOI
Deletion of LOX-1 Reduces Atherogenesis in LDLR Knockout Mice Fed High Cholesterol Diet
Jawahar L. Mehta,Nobuhito Sanada,Chang Ping Hu,Jiawei Chen,Abhijit Dandapat,Fumiaki Sugawara,Hiroo Satoh,Kazuhiko Inoue,Yosuke Kawase,Kou Ichi Jishage,Hiroshi Suzuki,Motohiro Takeya,Laura K. Schnackenberg,Richard D. Beger,Paul L. Hermonat,Maria Thomas,Tatsuya Sawamura +16 more
TL;DR: Generation of LOX-1 knockout mice in which binding of oxLDL to aortic endothelium was reduced and endothelia-dependent vasorelaxation preserved after treatment withOxLDL sustains endothelial function leading to a reduction in atherogenesis in association with reduction in proinflammatory and prooxidant signals.
Journal Article
Oxidative stress and ischemic myocardial syndromes.
TL;DR: The following aspects are covered: oxidative stress, mitochondrial dysfunction and pathophysiological mechanisms of atherosclerosis, precipitation of MI, sources of ROS in cardiac myocytes, effects of ROSIn the heart, and ischemia and reperfusion injuries and their mechanisms.