Low Concentration of Oxidized Low-Density Lipoprotein and Lysophosphatidylcholine Upregulate Constitutive Nitric Oxide Synthase mRNA Expression in Bovine Aortic Endothelial Cells

Hirata, Ken‐ichi; Miki, Nobuo; Kuroda, Yasuhiro; Sakoda, Tsuyoshi; Kawashima, Seinosuke; Yokoyama, Mitsuhiro

doi:10.1161/01.res.76.6.958

Cited by 139 publications

(86 citation statements)

References 35 publications

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“…On the other hand, LysoPC can also play an important antiatherogenic role by, in part, increasing the local synthesis of nitric oxide in the initial phases of the formation of atherosclerotic plaques, leading to vasodilation [44,45]. The antiatherogenic properties of LysoPC may also include its capacity to regulate macrophage-derived cholesterol homeostasis [46,47].…”

Section: Discussionmentioning

confidence: 99%

Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway

et al. 2016

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Edited by Laszlo NagyHere, we investigate the mechanism through which paraoxonase 1 (PON1) may regulate cholesterol efflux. Pretreatment of oxLDL with PON1 (oxLDL-PON1) contributed to the formation of LysoPC. In J774 macrophages, oxLDL-PON1 increased cholesterol efflux by more than 47% compared to oxLDL alone. oxLDL-PON1 significantly increased mRNA and protein expression of ABCA1 and ABCG1, as well as of PPARc and LXRa compared to oxLDL alone. Intraperitoneal injection of oxLDL-PON1-or LysoPC-treated J774 macrophages significantly increased the fecal elimination of macrophage-derived cholesterol in these mice. Our results suggest that PON1 stimulates cholesterol efflux via a mechanism that involves oxidized phospholipid hydrolysis.

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Section: Discussionmentioning

confidence: 99%

Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway

et al. 2016

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“…This effect is similar to the described response for lysoPC in other cultured endothelial cells. The role of lysoPC in the increased synthesis of e-NOS has been clarified in human umbilical vein endothelial cells and bovine arterial endothelial cells (18,19). Treatment of endothelial cells with lysoPC resulted in an increased transcription of the e-NOS mRNA in these cells, followed by an increased amount of protein and the corresponding activity.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, the lysoPC content of atherosclerotic arteries is higher than in normal vessels, and oxidized low-density lipoprotein displays a great proportion of lysoPC (17). LysoPC is able to increase the production of NO by endothelial cells by enhancing endothelial NO synthase (e-NOS) transcription (18,19), besides acting as an inhibitor of platelet aggregation (20). This evidence shows that lysoPC is potentially pro-atherogenic by inducing the production of several growth factors and the expression of chemoattractant genes (21).…”

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confidence: 99%

Lysophosphatidylcholine Acts as an Anti-hemostatic Molecule in the Saliva of the Blood-sucking Bug Rhodnius prolixus

Golodne

Monteiro

Graça-Souza

et al. 2003

Journal of Biological Chemistry

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Blood-sucking arthropods possess a variety of antihemostatic factors in their salivary glands to maintain blood fluidity during feeding. In this work we demonstrate the anti-hemostatic properties of lysophosphatidylcholine (lysoPC) isolated from the salivary glands of Rhodnius prolixus. First, we examined salivary glands of fourth and fifth instar nymphs for their phospholipid composition. The lumen displayed an accumulation of its phospholipid content, mainly phosphatidylcholine and lysoPC, with a 6-fold increase for the latter. To determine the presence of phospholipids in the saliva, fourth instar nymphs were fed with a 32 P-enriched blood meal. After 28 days their saliva was collected and subjected to lipid extraction, thin-layer chromatography, and autoradiography. The results showed the presence in the saliva of the same phospholipids present in the lumen. We then examined possible biological roles of these phospholipids when compared with other known effects of lysoPC. The luminal lipid extract and purified lysoPC from the lumen and saliva were tested for inhibition of washed rabbit platelets' aggregation induced by ␣-thrombin and platelet-activating factor. Both the luminal lipid extract and salivary lysoPC showed an increasing inhibition of aggregation, which correlated with the response of the platelets to standard lysoPC (up to 13 g/ml). Next, salivary lysoPC was incubated with porcine arterial endothelial cells for 24 h. After incubation, culture medium was assayed for nitric oxide and showed increased nitric oxide production, similar to control cells exposed to standard lysoPC (up to 20 g/ ml). Together these data demonstrate the presence of lysoPC in the saliva of Rhodnius prolixus and its potential anti-hemostatic activities.Hematophagous arthropods rely on a wide array of antihemostatic substances to counteract vertebrate responses to blood loss and to obtain their blood meal successfully (1). These salivary compounds show distinct properties and are generally involved with inhibition of coagulation, platelet aggregation, and vasoconstriction (2). These molecules include peptides such as tachykinins (3), maxadilan (4), nitric oxide (NO) 1 -binding proteins such as nitrophorins (5), and prostaglandins (6). The small lesions elicited by the mouthparts of the arthropod most likely evoke platelet aggregation and vasoconstriction by the vertebrate host. Therefore, the formation of the platelet plug is specifically inhibited by collagen inhibitors, apyrases, catechol oxidases, thrombin inhibitors, NO-releasing proteins, fibrinogen receptor agonists, and a specific platelet aggregation inhibitor (7,8). The complexity of anti-hemostatic mechanisms has recently been addressed with the use of proteomic techniques (9, 10). Hundreds of gene sequences were obtained, and most of them await future tests concerning the anti-hemostatic properties of the proteins they code for.Lysophosphatidylcholine (lysoPC) is a component of oxidized low-density lipoprotein, which is involved in the pathogenesis of atheroscleros...

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“…Evidence indicates that the increase in caveolin regulation in cells exposed to high levels of LDL-cholesterol results directly from an increase in the transcription of the eNOS gene induced by the higher cellular content of cholesterol 30 . In vitro studies have shown that, when endothelial cells are exposed to low concentrations of oxidized LDL (LDL-ox) for more than 24 hours, an increase in eNOS mRNA is observed, but in high concentrations of LDL-ox, this effect is reversed 31,32 . These observations show the existence of a correlation between the production of nitric oxide, hypercholesterolemia, and lipid peroxidation.…”

Section: Total Oxysterolsmentioning

confidence: 99%

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

Pereira

Bertolami

Faludi

et al. 2003

Arq. Bras. Cardiol.

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Original ArticleCardiovascular diseases are less prevalent in premenopausal women and in those receiving hormone replacement therapy as compared with postmenopausal women and men 1 . This protective effect is attributed to estrogens, and one of the mechanisms of action may be related to the metabolism of plasma lipoproteins 2 .Estrogens reduce LDL-cholesterol and increase HDLcholesterol 3 . However, these changes in lipid profile only contribute to approximately 25% of the protective effect of estrogens 4 . Other potential mechanisms of action of estrogens may include protection against LDL oxidation 5 , reduction in lipoprotein(a), potentiation of fibrinolysis 6 , and increase in insulin sensitivity. In the arteries, estrogens improve vasodilating function, decrease calcification, secretion of cell adhesion molecules (E-selectin, ICAM-1, and VCAM-1), and formation of atherosclerotic lesions 7 .Direct action of estrogens on the arterial wall has also been demonstrated. The administration of estrogens for prolonged periods inhibits the deposition of cholesterol in the arteries and thickening of the intima in monkeys and rabbits fed an atherogenic diet 8 . However, the mechanisms determining the direct effects of estrogens on the arterial wall have not been completely elucidated. The hemodynamic effects may be partially measured by the activity of estrogens on the synthesis of endothelial nitric oxide 9 . Estrogens have been suggested to possibly improve endothelial function and decrease the risks of atherosclerosis in premenopausal women. Nitric oxide has its bioactivity reduced in postmenopausal women. However, it is not clear whether this occurs due to its lower production by nitric oxide synthase, or whether nitric oxide is inactivated by reaction with the superoxide radical also generated by endothelial cells, forming the peroxynitrite anion (ONOO -), which is a strong oxidizing agent.Peroxynitrite is decomposed into other reactive oxygen species ( fig. 1) 10 and reacts with tyrosine residues of proteins to form nitrotyrosine 11 . Although little is known NOx, nitrotyrosine, COx, CE 18:2 -OOH, and PC-OOH were higher in the postmenopausal period (33.8±22.3 µM; 230±130 nM; 55±19 ng/µL; 17±8.7 nM; 2775±460 nM, respectively) Objective -To assess the effect of endogenous estrogens on the bioavailability of nitric oxide (·NO) and in the formation of lipid peroxidation products in pre-and postmenopausal women. Methods -NOx and S-nitrosothiols were determined by gaseous phase chemiluminescence, nitrotyrosine was determined by ELISA, COx (cholesterol oxides) by gas chromatography, and cholesteryl linoleate hydroperoxides (CE 18:2 -OOH), trilinolein (TG 18:2 -OOH), and phospholipids (PC-OOH) by HPLC in samples of plasma. Results -The concentrations of

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Low Concentration of Oxidized Low-Density Lipoprotein and Lysophosphatidylcholine Upregulate Constitutive Nitric Oxide Synthase mRNA Expression in Bovine Aortic Endothelial Cells

Cited by 139 publications

References 35 publications

Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway

Paraoxonase 1‐treated oxLDL promotes cholesterol efflux from macrophages by stimulating the PPARγ–LXRα–ABCA1 pathway

Lysophosphatidylcholine Acts as an Anti-hemostatic Molecule in the Saliva of the Blood-sucking Bug Rhodnius prolixus

Lipid peroxidation and nitric oxide inactivation in postmenopausal women

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