Effect of the oxidation state of LDL on the modulation of arterial vasomotor response in vitro.

Mougenot, Nathalie; Lesnik, Philippe; Ramirez‐Gil, Juan Fernando; Nataf, Patrick; Diczfalusy, Ulf; Chapman, M. John; Lechat, Philippe

doi:10.1016/s0021-9150(97)00124-x

Cited by 32 publications

(21 citation statements)

References 51 publications

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“…55 The content of 7␤-OH and 25-OH in LDL preparations, prepared in our laboratory under exactly the same oxidative conditions as in the current study, increased from initial levels of 7.8 and 5.7 ng/mg LDL protein, respectively, to 354 and 9.3 ng/mg LDL protein after 6 hours and to 41 284 and 878 ng/mg protein LDL after 48 hours of copper oxidation. 44 Such levels correspond to 4.1 g of 7␤-OH and 0.09 g of 25-OH per 100 g of oxLDL protein and were in the range of concentrations tested herein. Mattson Hultén et al 45 showed that both of these oxysterols were potent inhibitors of the expression of human macrophage LPL activity and mRNA mass, while under our conditions, only 7␤-OH had a biological effect.…”

Section: Time Course Of Evolution Of Oxidation Parameters and Phosphomentioning

confidence: 58%

“…LPO levels increased until 6 hours but decreased after 48 hours of LDL oxidation, in agreement with other authors who moreover reported a transient peak for LPO levels after 24 hours of LDL oxidation. 38,44 Expression of LPL activity by monocytes-macrophages was not modified by LDL oxidized for short periods (up to 2 hours) but increased slightly (25% of control) on incubation with LDL oxidized for 3 or 4 hours; enzyme activity declined in the presence of LDL oxidized 6 hours (ox 6 hours LDL), attaining levels (Ϫ31%) intermediate between those induced by native LDL (as the control) and by highly oxLDL (ox 48 hours LDL, Ϫ62%) ( Figure 5A). LPL mRNA levels were measured after incubation of macrophages with 2 hour-oxidized LDL (ox 2 hours LDL) and were similar to those detected under control conditions, whereas incubation with ox 6 hours LDL led to mRNA levels that were comparable with those obtained with ox 48 hours LDL (Ϫ70% and Ϫ45% of control levels) ( Figure 5B).…”

Section: Effect Of the Degree Of Oxidation Of Ldl On Macrophage Lpl Amentioning

confidence: 99%

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Inhibition of LPL Expression in Human Monocyte–Derived Macrophages Is Dependent on LDL Oxidation State

Stengel

Antonucci

Gaoua

et al. 1998

ATVB

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Abstract-The regulation of macrophage lipoprotein lipase (LPL) secretion and mRNA expression by atherogenic lipoproteins is of critical relevance to foam cell formation. LPL is present in arterial lesions and constitutes a bridging ligand between lipoproteins, proteoglycans, and cell receptors, thus favoring macrophage lipoprotein uptake and lipid accumulation. We investigated the effects of native and of oxidized lipoproteins on the expression of LPL in an in vitro human monocyte-macrophage system. Exposure of mature macrophages (day 12) to highly copper-oxidized human low density lipoprotein (LDL) (100 g protein per milliliter) led to marked reduction in the expression of LPL activity (Ϫ62%, PϽ0.01) and mRNA level (Ϫ47%, PϽ0.05); native LDL, acetylated LDL, and LDL oxidized for Ͻ6 hours were without effect. The reduction in LPL activity became significant at a threshold of 6 hours of LDL oxidation (Ϫ31%, PϽ0.05). Among the biologically active sterols formed during LDL oxidation, only 7␤-hydroxycholesterol (5 g/mL) induced a minor reduction in macrophage LPL activity, whereas 25-hydroxycholesterol was without effect. By contrast, lysophosphatidylcholine, whose LDL content increased in parallel with the degree of oxidation, induced significant reductions in LPL activity and mRNA levels at concentrations of 2 to 20 mol/L (Ϫ34% to Ϫ53%, PϽ0.01).Our results demonstrate that highly oxidized LDL (Ͼ6-hour oxidation) exerts negative feedback on LPL secretion in human monocytes-macrophages via a reduction in mRNA levels. By contrast, native LDL and mildly oxidized LDL (Ͻ6-hour oxidation) did not exert a feedback effect on LPL expression. We speculate that the content of lysophosphatidylcholine and, to a lesser degree, of 7␤-hydroxycholesterol in oxidized LDLs is responsible for the downregulation of LPL activity and mRNA abundance in human monocyte-derived macrophages and may therefore modulate LPL-mediated pathways of lipoprotein uptake during conversion of macrophages to foam cells. 2-5The mechanism of the conversion of macrophages to foam cells containing large amounts of cholesterol, cholesteryl esters, and TGs is presently the subject of extensive investigation. 6 The uptake of lipoproteins by such cells involves several receptors of distinct specificity, including scavenger receptors, 7 CD36, 8 and Fc receptors 9 for oxLDL; the LDL receptor; the LDL receptor-related protein receptor 10,11 ; the VLDL receptor for TG-rich lipoproteins 12 ; and last, membrane-binding proteins for uptake of certain TG-rich lipoproteins. 13 These cellular uptake mechanisms are rendered complex by the contribution of additional factors such as heparan sulfate proteoglycans of the matrix and cell plasma membranes and equally by LPL, 14 which may serve to "anchor" lipoproteins to the cell surface.LPL is a key enzyme of lipoprotein metabolism that hydrolyzes the TG component of chylomicrons and VLDL. 15 Moreover, LPL can act as a ligand to create a "bridge" between TG-rich lipoproteins and several receptors of the LDL family.16 LPL may al...

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Section: Time Course Of Evolution Of Oxidation Parameters and Phosphomentioning

confidence: 58%

Section: Effect Of the Degree Of Oxidation Of Ldl On Macrophage Lpl Amentioning

confidence: 99%

Inhibition of LPL Expression in Human Monocyte–Derived Macrophages Is Dependent on LDL Oxidation State

Stengel

Antonucci

Gaoua

et al. 1998

ATVB

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“…[85,86] Elevated serum cholesterol level is known to be associated with impaired endothelial function both in vivo and in vitro and may induce superoxide formation. [87,88] When kidney fails, hepatic apo-A-I synthesis decreases, and high density lipoproteins (HDL) levels fall. [89] HDL is an important antioxidant and defends the endothelium from the effects of cytokines.…”

Section: Discussionmentioning

confidence: 99%

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

Korish

2010

Renal Failure

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The kidney is an important source of L-arginine, the endogenous precursor of nitric oxide (NO). Surgical problems requiring extensive renal mass reduction (RMR) decrease renal NO production, leading to multiple hemodynamic and homeostatic disorders manifested by hypertension, oxidative stress, and increased inflammatory cytokines. Using the RMR model of chronic renal failure (CRF), we assessed the effects of twelve weeks' administration of L-arginine and/or a mixture of antioxidants (L-carnitine, catechin, vitamins E and C) on plasma cytokines, soluble intercellular adhesion molecule-1 (sICAM-1), nitrate and nitrites (NO 2 /NO 3 ), lipid profile, blood pressure, and renal function. CRF rats showed increased plasma IL-1a, IL1-b, IL-6, TNF-a, and sICAM-1 levels and decreased anti-inflammatory cytokines IL-4 and 10 levels, hypertension, and dyslipidemia. L-arginine treatment improved kidney functions, decreased systolic blood pressure, and decreased inflammatory cytokines levels. Antioxidants administration decreased inflammatory cytokines and sICAM-1 levels and increased IL-4 levels. Combined use of both L-arginine and the antioxidant mixture were very effective in their tendency to recover normal values of kidney functions, plasma cytokines, sICAM-1, blood pressure, NO 2 /NO 3 , cholesterol, and triglycerides concentrations. Indeed, the effects of L-arginine and the antioxidants on the reduction of proinflammatory cytokines may open new perspectives in the treatment of uremia.

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“…In previous studies, a high level of LDL cholesterol has been shown to inhibit endothelium-dependent vasodilatation in both humans (25) and rats (18). LDL can impair the vascular production of NO (25) or increase the generation of superoxide anion, which reacts with NO to form peroxynitrate, which in turn may play a significant role in oxidative tissue damage (20,36).…”

Section: Discussionmentioning

confidence: 95%

“…Calcium supplementation has also been reported to reduce plasma cholesterol levels, probably because orally ingested calcium binds bile acids and saturated fatty acids in the intestine (14,34,37). Elevated plasma cholesterol level is known to be associated with impaired endothelial function in both humans (6) and in rats (10,18,21). However, the effects of high calcium intake on plasma lipid profile and resistance vessel function in renal failure are unknown.…”

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confidence: 99%

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure

Jolma¹,

Kööbi²,

Kalliovalkama³

et al. 2003

American Journal of Physiology-Heart and Circulatory Physiology

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Chronic renal failure (CRF) is associated with abnormal lipid metabolism and high prevalence of vascular complications. Calcium salts are commonly used in CRF as phosphate binders. Increased calcium intake may also lower plasma cholesterol and beneficially influence vascular tone. Therefore, we investigated the influence of increasing dietary calcium from 0.3% to 3.0% for 8 wk after 5/6 nephrectomy (NTX) on plasma cholesterol and mesenteric resistance vessel tone in male Sprague-Dawley rats. The groups were Sham, Sham-Calcium, NTX, and NTX-Calcium ( n = 10–11). Blood pressure was modestly elevated after NTX, whereas the plasma creatinine, urea nitrogen, phosphate, and parathyroid hormone levels were clearly increased. The high-calcium diet suppressed plasma phosphate and parathyroid hormone but was without effect on blood pressure. The NTX resulted in 1.6-fold elevation in plasma total cholesterol and 40% reduction in high density-to-low density lipoprotein ratio (HDL/LDL). However, the lipid profile in NTX rats on the high-calcium diet did not differ from sham-operated controls. The endothelium-mediated relaxations induced by acetylcholine were impaired in NTX rats, whereas the response was normalized by a high-calcium diet. No differences in vasorelaxations by the endothelium-independent vasodilator nitroprusside were detected. In conclusion, improved vasorelaxation after a high-calcium diet could be due to reduced plasma total cholesterol and ameliorated HDL/LDL ratio, although decreased plasma phosphate and parathyroid hormone may also play a significant role in the vascular effects of increased calcium intake.

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Effect of the oxidation state of LDL on the modulation of arterial vasomotor response in vitro.

Cited by 32 publications

References 51 publications

Inhibition of LPL Expression in Human Monocyte–Derived Macrophages Is Dependent on LDL Oxidation State

Inhibition of LPL Expression in Human Monocyte–Derived Macrophages Is Dependent on LDL Oxidation State

Multiple Antioxidants and L-Arginine Modulate Inflammation and Dyslipidemia in Chronic Renal Failure Rats

Increased calcium intake reduces plasma cholesterol and improves vasorelaxation in experimental renal failure

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