Oxidized low-density lipoprotein increases the production of intracellular reactive oxygen species in endothelial cells

Cominacini, Luciano; Garbin, Ulisse; Pasini, Anna Fratta; Davoli, A.; Campagnola, M.; Pastorino, Antonio M.; Gaviraghi, G.; Cascio, Vincenzo Lo

doi:10.1097/00004872-199816121-00010

Cited by 83 publications

(52 citation statements)

References 39 publications

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“…31,32 Antioxidant activity has also been reported for other CCBs, 26,33,34 including lacidipine, a compound with which activity was observed in preclinical models of atherosclerotic disease, as well as in hypertensive patients, in whom a beneficial effect on carotid intima-media thickness and number of plaques was demonstrated.…”

Section: Antioxidant Properties Of Ccbsmentioning

confidence: 89%

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Mason

Marché

Hintze

2003

ATVB

156

117

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Abstract-Calcium channel blockers (CCBs) were developed as vasodilators, and their use in cardiovascular disease treatment remains largely based on that mechanism of action. More recently, with the evolution of second-and third-generation CCBs, pleiotropic effects have been observed, and at least some of CCBs' benefit is attributable to these mechanisms. Understanding these effects has contributed greatly to elucidating disease mechanisms and the rationale for CCB use. Furthermore, this knowledge might clarify why drugs are useful in some disease states, such as atherosclerosis, but not in others, such as heart failure. Although numerous drugs used in the treatment of vascular disease, including statins and angiotensin-converting-enzyme inhibitors, have well-described pleiotropic effects universally accepted to contribute to their benefit, little attention has been paid to CCBs' potentially similar effects.Accumulating evidence that at least 1 CCB, amlodipine, has pharmacologic actions distinct from L-type calcium channel blockade prompted us to investigate the pleiotropic actions of amlodipine and CCBs in general. There are several areas of research; foci here are (1) the physicochemical properties of amlodipine and its interaction with cholesterol and oxidants; (2) the mechanism by which amlodipine regulates NO production and implications; and (3) amlodipine's role in controlling smooth muscle cell proliferation and matrix formation.

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Section: Antioxidant Properties Of Ccbsmentioning

confidence: 89%

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Mason

Marché

Hintze

2003

ATVB

156

117

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“…It has been reported that patients with acromegaly have increased plasma concentrations of cholesterol [22], lipoprotein (a) and small dense LDL [23,24], and patients with hypercholesterolemia have impaired endothelium-dependent vasodilatation [25,26]. In fact, it has been shown that oxidized LDL-C impairs NO production [27], which plays a key role in the development of endothelial dysfunction and atherosclerosis [28] by production of reactive oxygen species [29].…”

Section: Discussionmentioning

confidence: 99%

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

et al. 2008

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Abstract. Flow-mediated vasodilatation (FMD) is a vascular functional test to detect endothelial dysfunction at the early stage of cardiovascular diseases. Patients with active acromegaly have higher morbidity and mortality due to cardiovascular events. To determine whether active acromegaly is associated with endothelial dysfunction, we studied 17 patients with active acromegaly for measurements of FMD, carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV), and other biochemical parameters before and 3 months after transsphenoidal surgery (TSS). Baseline %FMD in patients with active acromegaly was significantly lower than that in age-and sex-matched control subjects. After TSS, the mean %FMD in acromegaly significantly increased from 5.3% to 7.4%; 12 patients had increased %FMD (responders), whereas 5 patients had decreased or unchanged %FMD (non-responders). However, neither carotid IMT nor baPWV changed after TSS. Serum levels of GH, insulin-like growth factor (IGF)-1, total cholesterol, lowdensity lipoprotein cholesterol (LDL-C), hemoglobin HA1C, fasting plasma glucose and insulin levels, and homeostasis model assessment (HOMA)-R significantly decreased, whereas high-density lipoprotein cholesterol significantly increased. Responders had significantly lower baseline %FMD than did non-responders and both insulin levels and HOMA-R significantly decreased in responders, but not in non-responders after TSS. Simple regression analysis revealed that the change of %FMD showed a significant negative correlation with that of LDL-C, but not of IGF-1 or GH, in responders. In conclusion, it is suggested that endothelial dysfunction associated with active acromegaly improves soon after TSS, which is related to LDL-C and/or insulin resistance, but not to excess GH and/or IGF-1 itself.

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“…Samples were washed twice with PBS containing bovine serum albumin and analyzed with 10,000 cells/sample in flow cytometry (Coulter). The binding of di-15-ASP-labeled ox-LDL was expressed as mean fluorescence intensity (MFI) as described previously (37), and the data were fitted with GraFit (38). In our conditions, after incubation with ox-LDL, cell viability was always greater than 95%.…”

Section: Specific Binding Of Labeled Ox-ldl To Baecs and Blox-1-cho Cmentioning

confidence: 99%

Oxidized Low Density Lipoprotein (ox-LDL) Binding to ox-LDL Receptor-1 in Endothelial Cells Induces the Activation of NF-κB through an Increased Production of Intracellular Reactive Oxygen Species

Cominacini¹,

Pasini²,

Garbin³

et al. 2000

Journal of Biological Chemistry

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481

333

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In this study we examined the effect of oxidized low density lipoprotein (ox-LDL) on the intracellular production of reactive oxygen species (ROS) in bovine aortic endothelial cells (BAECs) and whether this increase occurs through its binding to the endothelial receptor lectin-like ox-LDL receptor-1 (LOX-1). Furthermore, this study also aimed to ascertain whether the binding of ox-LDL to LOX-1 is associated with NF-B activation. ox-LDL induced a significant dose-dependent increase in ROS production after a 30-s incubation with BAECs (p < 0.01). ROS formation was markedly reduced in BAECs incubated with anti-LOX-1 monoclonal antibody (p < 0.001), while control nonimmune IgG produced no effect. ox-LDL induced a time-and dose-dependent significant increase in ROS formation only in CHO-K1 cells stably expressing bovine LOX-1 (p < 0.001), while no increase was present in CHO-K1 cells. The activation of the transcription factor NF-B in BAECs was evident after a 5-min incubation with ox-LDL and was attenuated by anti-LOX-1 monoclonal antibody. The conclusion is that one of the pathophysiological consequences of ox-LDL binding to LOX-1 may be the activation of NF-B through an increased ROS production.

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Oxidized low-density lipoprotein increases the production of intracellular reactive oxygen species in endothelial cells

Cited by 83 publications

References 39 publications

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Novel Vascular Biology of Third-Generation L-Type Calcium Channel Antagonists

Improvement of Endothelial Dysfunction in Acromegaly after Transsphenoidal Surgery

Oxidized Low Density Lipoprotein (ox-LDL) Binding to ox-LDL Receptor-1 in Endothelial Cells Induces the Activation of NF-κB through an Increased Production of Intracellular Reactive Oxygen Species

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