Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice

Choi, Sung‐E; Jang, Hyun-Ju; Kang, Yup; Jung, Jo Won; Han, Seung Jin; Kim, Hae Jin; Kim, Dae Jung; Lee, Kwan‐Woo

doi:10.1016/j.vph.2010.09.004

Cited by 46 publications

(40 citation statements)

References 37 publications

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“…As described before, LiCl has also been proposed to be beneficial in atherosclerosis and has been used in rabbit model to reduce macrophage load in atherosclerotic plaques (De Meyer et al, 2011). A similar effect was found in a mouse model of atherosclerosis using high fat diet in ApoE knockout mice (Choi et al, 2010). Recent studies have also shown that LiCl decreases the severity of corneal disease (induced by Pseudomonas aeruginosa) by reducing inflammatory response and bacterial load.…”

Section: Effects Of LI In Inflammatory Disease Modelssupporting

confidence: 75%

Regulation of Macrophage Biology by Lithium: A New Look at an Old Drug

Raghavendra

Lee

Parameswaran

2013

J Neuroimmune Pharmacol

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Lithium (Li) continues to be a standard small compound used for the treatment of neurological disorders. Besides neuronal cells, Li is also known to affect immune cell function. In spite of its clinical use, potential mechanisms by which Li modulates immune cells, especially macrophages and its clinical relevance in bipolar patients are not well understood. Here, we provide an overview of the literature with regard to Li's effects on monocytes and macrophages. We have also included some of our results showing that Li differentially modulates chemokine gene expression in the absence and presence of Toll-like receptor-4 stimulation in a human macrophage model. Given that Li has a wide range of intracellular targets both in macrophages as well as in other cell types, more studies are needed to further understand the mechanistic basis of Li's effect in neurological and other inflammatory diseases. These studies could undoubtedly identify new therapeutic targets for treating such diseases.

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Section: Effects Of LI In Inflammatory Disease Modelssupporting

confidence: 75%

Regulation of Macrophage Biology by Lithium: A New Look at an Old Drug

Raghavendra

Lee

Parameswaran

2013

J Neuroimmune Pharmacol

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“…[19][20][21] These studies were unable to differentiate whether GSK3α/β's role in atherosclerosis was because of alterations in peripheral tissue, such as the liver or adipose, or local alterations within the vessel wall. In this report, we clearly show that GSK3α plays a local role in myeloid cells within the aortic wall during atherosclerosis development.…”

Section: Discussionmentioning

confidence: 99%

“…In mouse models, pharmacological inhibition of GSK3α/β or whole-body GSK3α deletion attenuates atherosclerotic lesion formation and the development of hepatic steatosis. [19][20][21] Although suggestive of a role for GSK3α/β in atherosclerosis, the homolog-and tissue-specific functions of GSK3α and GSK3β, as well as the mechanism by which GSK3α/β regulates atherosclerosis, are not known.…”

Section: Arterioscler Thromb Vasc Biolmentioning

confidence: 99%

Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype

McAlpine

Huang

Emdin

et al. 2015

ATVB

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A therosclerosis is the main underlying pathology of cardiovascular disease, which accounts for the majority of deaths in developed nations.1 Myeloid lineage cells are critical mediators in the development of atherosclerosis and account for the majority of a lesion's cellular bulk.2 Within the atherosclerotic lesion, macrophages phagocytose modified lipid particles becoming lipid engorged foam cells. Foam cells exacerbate disease progression through the secretion of proinflammatory cytokines and growth factors. In advanced lesions, foam cells undergo apoptosis leading to the formation of a lipid-rich, acellular, and highly thrombotic necrotic core. The underlying molecular mechanisms that regulate myeloid cell behavior during atherosclerosis remain poorly defined.Increasing evidence suggests that myeloid cell subpopulations are heterogeneous and have distinctive phenotypes that play unique roles in disease states. Macrophages are often broadly classified as having a classical (M1) or an alternative (M2) phenotype. M1 macrophages, elicited by toll-like receptor or interferon-γ receptor stimulation, are the most prominent macrophages at sites of inflammation and exacerbate the inflammatory response through the secretion of proinflammatory cytokines and chemoatractants.3,4 M1 macrophages promote atherosclerotic lesion development and complexity.5-7 M2 macrophages patrol tissue, perform reparative and immunoregulatory functions, efferocytose debris, and are antiatherogenic. 3,4,8 Other macrophage subtypes have been identified in atherosclerotic lesions, including M4, Mox, and Mhem; however, their roles are less well characterized. 3,5,9,10 Our understanding of the cellular signaling networks that regulate macrophage polarization in the context of atherosclerosis and the relative contribution of each phenotype to the progression and development of atherosclerosis is limited.Glycogen synthase kinase (GSK)-3 α and β are homologous serine/threonine kinases encoded by separate genes. 11GSK3α and GSK3β share 98% amino acid homology within their kinase domain but only 36% homology in the C-terminal domain. GSK3α (51 kDa) is 5 kDa larger than GSK3β (46 kDa) because of an N-terminal glycine-rich domain with an © 2015 American Heart Association, Inc. Objective-Glycogen synthase kinase (GSK)-3α/β has been implicated in the pathogenesis of diabetes mellitus, cancer, Alzheimer, and atherosclerosis. The tissue-and homolog-specific functions of GSK3α and β in atherosclerosis are unknown. This study examines the effect of hepatocyte or myeloid cell deletion of GSK3α or GSK3β on atherosclerosis in low-density lipoprotein receptor (LDLR) −/− mice. Approach and Results-We ablated GSK3α or GSK3β expression in hepatic or myeloid cells of LDLR −/− mice, and mice were fed a high-fat diet for 10 weeks. GSK3α or GSK3β deficiency in hepatic or myeloid cells did not affect metabolic parameters, including plasma lipid levels. Hepatic deletion of GSK3α or GSK3β did not affect the development of atherosclerosis or hepatic lipid content. Myeloid ...

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“…In vivo studies have also demonstrated a role for GSK3 ␣ / ␤ in the regulation of NF-B ( 29 ). Furthermore, our group and others have shown that inhi bition of GSK3 ␣ / ␤ is associated with attenuated atherosclerotic development and reduced hepatic steatosis in different mouse models ( 7,30,31 ). However, the mechanisms by which ER stress modulates GSK3 ␣ and/or ␤ , and how GSK3 ␣ / ␤ regulates proatherogenic processes, remain unresolved.…”

Section: Immunoblotmentioning

confidence: 97%

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

McAlpine

Werstuck²

2014

Journal of Lipid Research

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This article is available online at http://www.jlr.org cause of cerebrovascular and cardiovascular diseases, which together account for a third of all deaths in Western societies ( 1, 2 ). Multiple risk factors contribute to the initiation and progression of atherosclerosis including diabetes mellitus, hypertension, obesity, dyslipidemia, a sedentary life style, and smoking ( 3 ). One of the hallmark features of every stage of atherogenesis, from the fatty streak to the complex plaque, is the presence of lipid-laden macrophages known as foam cells. Intimal macrophage/foam cells accumulate lipids from LDL and modifi ed LDL particles and secrete a variety of infl ammatory cytokines. In advanced plaques, foam cells undergo apoptosis, thereby contributing to the formation of a highly thrombotic, lipid rich, necrotic core [reviewed by Moore and Tabas ( 4 )]. The molecular events that promote the initiation and development of atherosclerosis are poorly understood. A better understanding of the signaling networks that regulate foam cell formation and atherosclerotic plaque development may lead to the identifi cation of novel therapeutic targets.The endoplasmic reticulum (ER) is the organelle responsible for the proper folding, modifi cation, and processing of secretory, transmembrane, and ER resident proteins. If the processing capacity of the ER is overwhelmed, unfolded or misfolded proteins begin to accumulate, a condition known as ER stress. The accumulation of misfolded proteins triggers the initiation of the unfolded protein response (UPR), which is composed of three signaling cascades regulated by ER transmembrane Atherosclerosis is an infl ammatory disease within the walls of medium and large arteries ( 1 ). It is the leading C. S.

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Atherosclerosis induced by a high-fat diet is alleviated by lithium chloride via reduction of VCAM expression in ApoE-deficient mice

Cited by 46 publications

References 37 publications

Regulation of Macrophage Biology by Lithium: A New Look at an Old Drug

Regulation of Macrophage Biology by Lithium: A New Look at an Old Drug

Deletion of Myeloid GSK3α Attenuates Atherosclerosis and Promotes an M2 Macrophage Phenotype

Protein kinase R-like endoplasmic reticulum kinase and glycogen synthase kinase-3α/β regulate foam cell formation

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