Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease

Vascular Health and Risk Management, Journal Year: 2016, Volume and Issue: unknown, P. 171 - 171

Published: May 1, 2016

Abstract: Approximately 25% of US adults are estimated to have hypertriglyceridemia (triglyceride [TG] level ≥150 mg/dL [≥1.7 mmol/L]). Elevated TG levels associated with increased cardiovascular disease (CVD) risk, and severe (TG ≥500 [≥5.6 mmol/L]) is a well-established risk factor for acute pancreatitis. Plasma correspond the sum content in TG-rich lipoproteins (TRLs; ie, very low-density plus chylomicrons) their remnants. There remains some uncertainty regarding direct causal role TRLs progression atherosclerosis CVD, outcome studies TG-lowering agents, date, having produced inconsistent results. Although lipoprotein cholesterol (LDL-C) primary treatment target reduce CVD number large-scale epidemiological shown that elevated independently incidence events, even patients treated effectively statins. Genetic further clarified association between CVD. Variants several key genes involved TRL metabolism strongly strength variant's effect on correlating magnitude thought contribute via indirect mechanisms. They directly intimal deposition also activation enhancement proinflammatory, proapoptotic, procoagulant pathways. Evidence suggests non-high-density cholesterol, total carried by atherogenic (including LDL, TRL, remnants), provides better indication than LDL-C, particularly hypertriglyceridemia. This article aims provide an overview available epidemiological, clinical, genetic evidence relating atherogenicity Keywords: triglycerides, non-highdensity, hypertriglyceridemia, lipase, chylomicrons,

Language: Английский

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Postprandial lipoproteins and the molecular regulation of vascular homeostasis

Progress in Lipid Research, Journal Year: 2013, Volume and Issue: 52(4), P. 446 - 464

Published: June 15, 2013

Language: Английский

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Identification of the Oxidized Low-Density Lipoprotein Scavenger Receptor CD36 in Plasma

Circulation, Journal Year: 2006, Volume and Issue: 114(11), P. 1169 - 1176

Published: Sept. 5, 2006

Background— Macrophage CD36 scavenges oxidized low-density lipoprotein, leading to foam cell formation, and appears be a key proatherogenic molecule. Increased expression of has been attributed hyperglycemia defective macrophage insulin signaling in resistance. Premature atherosclerosis is the major cause morbidity mortality type 2 diabetes. Here, we report identification soluble form (sCD36) plasma hypothesize that sCD36 would elevated patients with diabetes Methods Results— was demonstrated by immunopurification Western blotting. We established ELISA assays determine measured obese diabetic patients, nondiabetic relatives, lean control subjects. markedly compared both (5-fold) (2- 3-fold) There strong, inverse correlation between insulin-stimulated glucose disposal direct fasting glucose, insulin, body mass index. Conclusions— Our study demonstrates for first time. highly related risk factors accelerated such as resistance glycemic control, propose might represent marker metabolic syndrome potential surrogate atherosclerosis.

Language: Английский

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Lipolysis of triglyceride-rich lipoproteins, vascular inflammation, and atherosclerosis

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2011, Volume and Issue: 1821(5), P. 858 - 866

Published: Oct. 14, 2011

Language: Английский

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Oxidative stress influences cholesterol efflux in THP-1 macrophages: Role of ATP-binding cassette A1 and nuclear factors☆

Cardiovascular Research, Journal Year: 2006, Volume and Issue: 72(3), P. 473 - 482

Published: Sept. 15, 2006

Understanding the mechanisms involved in oxidative stress-induced foam cell formation is of fundamental importance for atherosclerosis. Our aim was to characterize effects stress on key receptors macrophage cholesterol homeostasis, nuclear transcription factors PPAR and LXR regulating their expression, handling.The incubation macrophages derived from human monocyte line THP-1 with iron (100 microm)/ascorbate (1000 microm) a period 4 h induced strong peroxidation, as demonstrated by elevation malondialdehyde (220%, P < 0.001). The production lipid peroxidation affected efflux, which probably due decreased ABCAI gene protein expression. On other hand, influx remained unchanged did mRNA levels SR-BI CD36, important that participate import. Experiments using RT-PCR showed modulation orchestrated LXRalpha, LXRbeta, PPARalpha, PPARgamma. Treatment powerful antioxidants (Trolox BHT) prevented adverse iron-ascorbate movement, conceivably supporting role stress.Our results show can directly be concomitantly impairs expression flux, could influence atherosclerosis development.

Language: Английский

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The induction of macrophage foam cell formation by chylomicron remnants

Biochemical Society Transactions, Journal Year: 2007, Volume and Issue: 35(3), P. 454 - 458

Published: May 22, 2007

The accumulation of foam cells in the artery wall causes fatty streaks, first lesions atherosclerosis. LDL (low-density lipoprotein) plays a major role cell formation, although prior oxidation particles is required. Recent studies, however, have provided considerable evidence to indicate that CMRs (chylomicron remnants), which carry dietary lipids blood, induce formation without oxidation. We shown are taken up by macrophages and both triacylglycerol cholesterol, rate uptake amount lipid accumulated influenced type fat particles. Furthermore, CMRs, striking contrast with LDL, inhibits, rather than enhances, their induction accumulation. In addition, after exposure resistant efflux, this may be due its sequestration lysosomes. These findings demonstrate pro-atherogenic changes macrophages, effects modulated factors including oxidized fats, lipophilic antioxidants present.

Language: Английский

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Residual cardiovascular risk of lipid origin. Components and pathophysiological aspects

Clínica e Investigación en Arteriosclerosis (English Edition), Journal Year: 2019, Volume and Issue: 31(2), P. 75 - 88

Published: March 1, 2019

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Effects of lycopene on the induction of foam cell formation by modified LDL

AJP Endocrinology and Metabolism, Journal Year: 2007, Volume and Issue: 293(6), P. E1820 - E1827

Published: Oct. 3, 2007

The effect of lycopene on macrophage foam cell formation induced by modified low-density lipoprotein (LDL) was studied. Human monocyte-derived macrophages (HMDM) were incubated with in the presence or absence native LDL (nLDL) oxidation (oxLDL), aggregation (aggLDL), acetylation (acLDL). cholesterol content, lipid synthesis, scavenger receptor activity, and secretion inflammatory [interleukin (IL)-1beta tumor necrosis factor (TNF)-alpha] anti-inflammatory (IL-10) cytokines determined. Lycopene found to decrease synthesis ester incubations without oxLDL while triacylglycerol reduced aggLDL. Scavenger activity as assessed uptake acLDL decreased approximately 30% lycopene. In addition, inhibited IL-10 up 74% regardless nLDL aggLDL but did not affect IL-1beta TNF-alpha release. also relative abundance mRNA transcripts for A (SR-A) THP-1 treated These findings suggest that may reduce decreasing downregulating expression SR-A. However, these effects are accompanied impaired cytokine IL-10, suggesting exert a concomitant proinflammatory effect.

Language: Английский

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Human native lipoprotein-induced de novo DNA methylation is associated with repression of inflammatory genes in THP-1 macrophages

BMC Genomics, Journal Year: 2011, Volume and Issue: 12(1)

Published: Nov. 25, 2011

Abstract Background We previously showed that a VLDL- and LDL-rich mix of human native lipoproteins induces set repressive epigenetic marks, i.e. de novo DNA methylation, histone 4 hypoacetylation lysine 20 (H4K20) hypermethylation in THP-1 macrophages. Here, we: 1) ask what gene expression changes accompany these responses; 2) test the involvement candidate factors mediating latter. exploited genome arrays to identify target genes for lipoprotein-induced silencing, addition RNAi studies factors. The study was conducted Results Native methylation associated with general repression various critical macrophage function, including pro-inflammatory genes. Lipoproteins differential effects on as induced by VLDL lesser extent LDL, but not HDL, H4K20 hypermethylation, while HDL caused H4 deacetylation. analysis VLDL-induced revealed this response was: surprisingly, mediated exclusively canonical maintenance methyltransferase DNMT1, independent Dicer/micro-RNA pathway. Conclusions Our work provides novel insights into regulation lipoproteins. Furthermore, we provide an example DNMT1 acting independently enzymes, show proof principle can occur functional pathway mammals.

Language: Английский

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The iterative lipid impact on inflammation in atherosclerosis

Current Opinion in Lipidology, Journal Year: 2021, Volume and Issue: 32(5), P. 286 - 292

Published: Aug. 16, 2021

Lipid-mediated atherogenesis is hallmarked by a chronic inflammatory state. Low-density lipoprotein cholesterol (LDL-C), triglyceride rich lipoproteins (TRLs), and lipoprotein(a) [Lp(a)] are causally related to atherosclerosis. Within the paradigm of endothelial activation subendothelial lipid deposition, these induce numerous pro-inflammatory pathways. In this review, we will outline effects on systemic pathways in atherosclerosis.Apolipoprotein B-containing exert variety effects, ranging from local artery immune cell activation. LDL-C, TRLs, Lp(a) dysfunction with concomitant circulating monocytes through enhanced accumulation. The process trained immunity innate system, predominantly induced LDL-C particles, hallmarks propagation low-grade response. concert, bone marrow induces myeloid skewing, further contributing mobilization plaque progression.Lipoproteins inflammation intertwined atherogenesis. Elucidating provide new opportunities for therapeutic agents.

Language: Английский

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