Inflammation and diabetes-accelerated atherosclerosis: myeloid cell mediators

Kanter, Jenny E.; Bornfeldt, Karin E.

doi:10.1016/j.tem.2012.10.002

Cited by 54 publications

(48 citation statements)

References 58 publications

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“…Surprisingly, the deficiency caused a reduction in the levels of 20:4ω6-CoA and blocked the increased production of PGE 2 that is usually observed in mice with type-1 diabetes. It was speculated that this finding was the result of either limited uptake and activation of 20:4 with depletion of the membrane phospholipid pool available as a substrate for phospholipase A2 (83) or was caused by lack of ACSL1-mediated activation of 18:2 as a substrate for the elongation and desaturation enzymes that convert 18:2-CoA to 20:4-CoA (85). In addition, when macrophages are activated by a variety of inflammatory signals, Acsl1 mRNA and protein increase markedly (167).…”

Section: Long-chain Acyl-coa Synthetasesmentioning

confidence: 99%

Acyl-CoA Metabolism and Partitioning

Grevengoed¹,

Klett

Coleman³

2014

Annu. Rev. Nutr.

366

330

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Long-chain fatty acyl-CoAs are critical regulatory molecules and metabolic intermediates. The initial step in their synthesis is the activation of fatty acids by one of 13 long-chain acyl-CoA synthetase isoforms. These isoforms are regulated independently and have different tissue expression patterns and subcellular locations. Their acyl-CoA products regulate metabolic enzymes and signaling pathways, become oxidized to provide cellular energy, and are incorporated into acylated proteins and complex lipids like triacylglycerol, phospholipids, and cholesterol esters. Their differing metabolic fates are determined by a network of proteins that channel the acyl-CoAs towards or away from specific metabolic pathways and serve as the basis for partitioning. This review evaluates the evidence for acyl-CoA partitioning by reviewing experimental data on proteins that are believed to contribute to acyl-CoA channeling, the metabolic consequences of loss of these proteins, and the potential role of maladaptive acyl-CoA partitioning in the pathogenesis of metabolic disease and carcinogenesis.

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Section: Long-chain Acyl-coa Synthetasesmentioning

confidence: 99%

Acyl-CoA Metabolism and Partitioning

Grevengoed¹,

Klett

Coleman³

2014

Annu. Rev. Nutr.

366

330

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“…However, the published substrate preference for each ACSL family member is not invariably observed. For example, although the purified recombinant ACSL1 had no preference for arachidonate or linoleate, ACSL1 is critical for the synthesis of arachidonoyl-CoA in macrophages (73) and was inferred to prefer linoleate in the heart (74). Studies performed in different cell lines also reveal disparate effects of ACSL4 deficiency on arachidonic acid metabolism for phospholipid synthesis and prostaglandin secretion.…”

Section: Acsl Substrate Preferencementioning

confidence: 99%

Physiological Consequences of Compartmentalized Acyl-CoA Metabolism

Cooper

Young

Klett

et al. 2015

Journal of Biological Chemistry

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Meeting the complex physiological demands of mammalian life requires strict control of the metabolism of long-chain fatty acyl-CoAs because of the multiplicity of their cellular functions. Acyl-CoAs are substrates for energy production; stored within lipid droplets as triacylglycerol, cholesterol esters, and retinol esters; esterified to form membrane phospholipids; or used to activate transcriptional and signaling pathways. Indirect evidence suggests that acyl-CoAs do not wander freely within cells, but instead, are channeled into specific pathways. In this review, we will discuss the evidence for acyl-CoA compartmentalization, highlight the key modes of acyl-CoA regulation, and diagram potential mechanisms for controlling acylCoA partitioning.Two prevailing views of metabolic pathways within the cytosol are a) as sequential steps within a largely empty space with substrates and products traveling from one enzyme to the next, and b), as embedded within a dense network of proteins and metabolites, all jockeying for position. In contrast to these two views, it is likely that synthetic and degradative pathways are composed of enzymes and their regulators in highly organized multi-enzyme assemblies designed to enhance efficiency and regulate steady-state flux (1). Proteins within these assemblies might interact via their transmembrane and extra-membrane domains or be tethered to scaffolds, in a manner that is regulated by allosteric effectors and post-translational modifications (2, 3). Such interactions may be transient, as occurs with the enzymes that comprise purinosomes (4), or they may be semi-permanent as occurs within glycogen granules that contain enzymes that synthesize and degrade glycogen, and their regulatory kinases and phosphatases (5, 6). Assemblies of proteins are advantageous because even without a physical tunnel, they can increase reaction rates by enhancing local substrate concentrations, restricting intermediates from entering competing reactions, and stabilizing chemically unstable intermediates.Because the dysregulation of metabolic homeostasis has been implicated in a multitude of human diseases, acyl-CoA metabolism represents a critical node for understanding whole-body pathophysiology. Apart from eicosanoid synthesis, the first step in the metabolism of long-chain fatty acids (FAs) 2 is their thioesterification. The resulting acyl-CoA is then metabolized by one of six major enzyme families: elongases and desaturases (7), dehydrogenases (8, 9), acyl-CoA thioesterases (10, 11), carnitine palmitoyltransferases (CPT) (12), and lipid and protein acyltransferases (13) (Fig. 1). These competing pathways, often present within a single subcellular compartment and coupled with the highly specialized metabolism of individual cells and tissues, suggest a level of organization extending beyond enzymatic function. In this review, we will use a physiological lens to focus on longchain mammalian fatty acyl-CoAs and the evidence for compartmentalized acyl-CoA metabolism.

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“…Т2DM patients are more likely to exhibit an accelerated development of atherosclerosis and have a 3-4-fold increased risk for cardiovascular mortality [2] . Hyperglycemia is currently considered the main culprit for vascular lesion progression.…”

Section: Introductionmentioning

confidence: 99%

Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease

Nikiforov¹,

Galstyan²,

Недосугова³

et al. 2017

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How to cite this article: Nikiforov NG, Galstyan KO, Nedosugova LV, Elizova NV, Kolmychkova KI, Ivanova EA. Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease. Vessel Plus 2017;1:192-5.Aim: Type 2 diabetes mellitus (T2DM) is associated with rapid progression of atherosclerosis. There is no doubt that inflammation is involved in atherogenesis. Recent studies showed the relationship between the development of atherosclerotic plaque formation and the amount of pro-inflammatory (M1) activated macrophages in situ. Methods: The authors studied the ability of circulating monocytes isolated from patients with diabetes (n = 28), coronary heart disease (CHD) (n = 27) and healthy subjects (n = 50) to be activated into M1 phenotype in vitro. Results: Increased levels of basal and stimulated secretion of tumor necrosis factor alpha (TNF-α) was observed in diabetic patients compared with healthy subjects. On the contrary, in patients with CHD, decreased secretion of the pro-inflammatory cytokine, TNF-α, was found. A direct correlation between glycated hemoglobin (HbA1c) levels in T2DM patients and basal secretion of TNF-α from monocytes was observed. Conclusion: The authors found diametrically different responses of monocytes from T2DM and CHD under pro-inflammatory stimuli. Key words:Type 2 diabetes mellitus, coronary heart disease, M1/M2 monocyte polarization, oxidative stress, atherosclerosis, inflammatory ABSTRACTArticle history:

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Inflammation and diabetes-accelerated atherosclerosis: myeloid cell mediators

Cited by 54 publications

References 58 publications

Acyl-CoA Metabolism and Partitioning

Acyl-CoA Metabolism and Partitioning

Physiological Consequences of Compartmentalized Acyl-CoA Metabolism

Proinflammatory monocyte polarization in type 2 diabetes mellitus and coronary heart disease

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