Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells

Gesquiere, Laurence R.; Loreau, Nadine; Minnich, Anne; Davignon, Jean; Blache, Denis

doi:10.1016/s0891-5849(99)00055-6

Cited by 75 publications

(51 citation statements)

References 46 publications

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“…The increase in plasma cholesterol may result from enhanced hepatic cholesterogenesis and/or reduced cholesterol clearance from the system, an effect that has been suggested for other metals (23,24). Furthermore, lower clearance of LDL precursor particles could result in a persistence of cholesterol, resulting in hypercholesterolemia (25).…”

Section: Discussionmentioning

confidence: 99%

Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

Afolabi

Oyewo

Adekunle

et al. 2013

Archives of Industrial Hygiene and Toxicology

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The aim of this study was to establish the effects of fl uoride on lipid metabolism and attendant infl ammatory response by exposing rats to 50 mg L -1 and 100 mg L -1 of fl uoride through drinking water for seven weeks. Both concentrations led to hypercholesterolemia while the 100 mg L -1 concentration induced hypertriglyceridaemia. High density lipoprotein (HDL) cholesterol levels dropped in the exposed rats while interleukin 2 (IL-2) increased more than 1.5-fold (p<0.05) and IL-6 and plasma TNF-α more than 2.5 fold (p<0.05). Fluoride-exposed rats also had signifi cantly higher levels of liver malondialdehyde (MDA) and plasma lipid hydroperoxide (LOOH) but lower plasma paraoxonase (PON1) activity. Oxidative stress indices correlated with pro-infl ammatory cytokines and plasma cholesterol. In contrast, proinfl ammatory cytokines inversely correlated with plasma triglyceride, HDL cholesterol and PON1. Our results suggest that the association between fl uoride exposure with cardiovascular diseases may be related to its ability to disturb lipid homeostasis, and trigger pro-infl ammatory cytokines and oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

Afolabi

Oyewo

Adekunle

et al. 2013

Archives of Industrial Hygiene and Toxicology

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“…Oxidative stress may be an important factor that promotes the kinds of derangements of cholesterol and sphingolipid metabolism that occur in AD. Studies of non-neuronal cells have shown that oxidative stress and ceramide production can increase the accumulation of cholesterol in cells (46)(47)(48)(49). High levels of free cholesterol can be toxic to cells as demonstrated by the ability of inhibitors of ACAT (an enzyme that converts free cholesterol to cholesterol esters) to induce apoptosis (31,50) and by the ability of statins to protect neurons against ischemic͞oxidative injury (51,52).…”

Section: Discussionmentioning

confidence: 99%

Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

Cutler

Kelly

Storie

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

992

854

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Alzheimer's disease (AD) is an age-related disorder characterized by deposition of amyloid ␤-peptide (A␤) and degeneration of neurons in brain regions such as the hippocampus, resulting in progressive cognitive dysfunction. The pathogenesis of AD is tightly linked to A␤ deposition and oxidative stress, but it remains unclear as to how these factors result in neuronal dysfunction and death. We report alterations in sphingolipid and cholesterol metabolism during normal brain aging and in the brains of AD patients that result in accumulation of long-chain ceramides and cholesterol. Membrane-associated oxidative stress occurs in association with the lipid alterations, and exposure of hippocampal neurons to A␤ induces membrane oxidative stress and the accumulation of ceramide species and cholesterol. Treatment of neurons with ␣-tocopherol or an inhibitor of sphingomyelin synthesis prevents accumulation of ceramides and cholesterol and protects them against death induced by A␤. Our findings suggest a sequence of events in the pathogenesis of AD in which A␤ induces membrane-associated oxidative stress, resulting in perturbed ceramide and cholesterol metabolism which, in turn, triggers a neurodegenerative cascade that leads to clinical disease.amyloid ͉ apoptosis ͉ hippocampus ͉ lipid peroxidation ͉ sphingomyelin C hanges that occur in the brain during aging increase the risk of Alzheimer's disease (AD), a disorder involving the progressive deposition of amyloid ␤-peptide (A␤) and associated degeneration of neurons in brain regions involved in learning and memory (1). Two factors that are believed to contribute to neuronal dysfunction and degeneration in AD are increased oxidative stress and increased production of neurotoxic forms of A␤ (2). Alterations in lipid metabolism may also play roles in AD because the risk of AD is affected by inheritance of different isoforms of apolipoprotein E (3), changes in cholesterol metabolism can affect A␤ production in cell culture and in vivo (4-6), and drugs that lower cholesterol levels may reduce the risk of AD (7,8). However, a direct link between alterations in the metabolism of cholesterol and other membrane lipids in AD has not been established, and it is not known whether and how such lipid alterations might lead to neuronal dysfunction and death.Membrane microdomains that are rich in cholesterol and sphingolipids play important roles in various cellular signaling pathways (9, 10). Sphingomyelin is a major source of ceramides, lipid mediators that are generated when sphingomyelin is cleaved by sphingomyelinases, enzymes activated by inflammatory cytokines (11) and oxidative stress (12). Ceramides play important roles in regulating an array of physiological processes, including cell proliferation and differentiation, and a form of programmed cell death called apoptosis (13). Ceramides have been implicated in the pathological death of neurons that occurs in ischemic stroke (14) and Parkinson's disease (15). In the present study, we document significant increases in levels of m...

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“…[14][15][16][17] Several mechanisms that, in part, explain these worse outcomes may also explain the development of PMI in patients with moderate renal failure. These mechanisms include: (1) excessive inflammatory response and oxidative stress, which may cause the myocardium to become vulnerable via additional inflammatory cells, resulting in apoptosis and myocardial necrosis; 18,19 (2) activation of the sympathetic nervous and renin angiotensin systems, resulting in vasoconstriction and increased angiotensin-2 levels; 20,21 (3) increased homocysteine and oxidative stress, resulting in more atherogenic plaque, 22,23 which may lead to platelet activation and thrombosis; and (4) platelet response to antithrombotic agents. 24 In our study, we also see high rates of CRP elevation in moderate RI; this may also show excessive inflammation in moderate RI and indicate one of the possible mechanisms of PMI.…”

Section: 6mentioning

confidence: 99%

Effect of estimated glomerular filtration rate on periprocedural myocardial infarction in patients undergoing elective percutaneous coronary intervention

et al. 2013

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Backgrounds: Little is known about the effect of the estimated glomerular filtration rate (eGFR) on the periprocedural myocardial infarction (PMI). The aim of this study was to determine an eGFR value that is related with PMI development in patients with stable angina undergoing elective percutaneous coronary intervention (PCI). Method: A retrospective analysis was conducted of 257 consecutive PCI patients with stable angina pectoris. The patients were divided into three groups according to eGFR: Group 1: eGFR490 mL/min/1.73 m

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Oxidative stress leads to cholesterol accumulation in vascular smooth muscle cells

Cited by 75 publications

References 46 publications

Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

Oxidative Indices Correlate with Dyslipidemia and Pro-Inflammatory Cytokine Levels in Fluoride-Exposed Rats

Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer's disease

Effect of estimated glomerular filtration rate on periprocedural myocardial infarction in patients undergoing elective percutaneous coronary intervention

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