Nitric Oxide Inhibition Enhances Platelet Aggregation in Experimental Anti-Thy-1 Nephritis

Goor, Harry van; Albrecht, Ester W.J.A.; Heeringa, Peter; Klok, Pieter; Horst, Marian L.C. van der; Jager-Krikken, Alie de; Bakker, Winston W.; Moshage, Han

doi:10.1006/niox.2001.0382

Cited by 15 publications

(8 citation statements)

References 23 publications

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“…First, one could wonder why an infusion of VEGF should have beneficial effects in models of renal disease (28,30,34,41) as many of these models are associated with some degree of endothelial dysfunction. However, there is supportive evidence that the degree of endothelial dysfunction is likely not severe in these models (28,34,56,70) and that the VEGF-NO axis is largely intact. Second, the role of NO is complicated in VEGF-induced endothelial cell proliferation since NO positively or negatively regulates endothelial cell proliferation in response to VEGF (4,55,78).…”

Section: Counterargumentsmentioning

confidence: 94%

Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease

Nakagawa

2007

American Journal of Physiology-Renal Physiology

122

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In many forms of experimental kidney diseases, renal VEGF is low, and administering VEGF can be shown to be protective. A paradox occurs in diabetes, in which renal VEGF levels are high and a deleterious effect of VEGF on kidney disease has been shown. We have hypothesized that endothelial dysfunction induced by hyperglycemia or other factors may underlie the pathogenic mechanisms of a high VEGF state. VEGF normally stimulates endothelial nitric oxide (NO) release and acts in concert with elevated NO levels as a trophic factor for vascular endothelium. The increased NO derived from the endothelial cell acts as an inhibitory factor that prevents excess endothelial cell proliferation, vascular smooth muscle cell proliferation, and macrophage infiltration. In the setting where NO bioavailability is reduced in diabetes, high levels of VEGF lead to excessive endothelial cell proliferation, stimulation of macrophage chemotaxis, and vascular smooth muscle cell activation. Consistent with this hypothesis is our recent observation that diabetes induced in endothelial NO-deficient mice results in clinical and histological features identical to human diabetic nephropathy. The discovery of the key role for impaired endothelial NO bioavailability in the stimulation of VEGF and VEGF-dependent disease may provide key insights into not only the pathogenesis of diabetic nephropathy but also the utility and hazard of administering VEGF as a treatment for kidney disease.

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Section: Counterargumentsmentioning

confidence: 94%

Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease

Nakagawa

2007

American Journal of Physiology-Renal Physiology

122

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“…Indeed, it has been discovered that NO in many biological processes functions to prevent platelet aggregation [2], and operates as a major defense molecule in immune cells [3] and intracellular bacterium [4], even though the NO at high concentrations has shown to be toxic [5 -9].…”

Section: Introductionmentioning

confidence: 99%

Simple Fabrication of Amperometric Nitric Oxide Microsensors Based on Electropolymerized Membrane Films

Shim

Lee

2010

Electroanalysis

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Demand for highly sensitive, selective, and practically reliable sensors which could be easily fabricated is increasing for various applications in biological and biomedical systems. Thus, here we present a novel and simple amperometric NO microsensor based on electropolymerized polymeric films. The sensor consists of a platinized Pt disk anode (25-mm diameter) which surface is modified with electropolymerized polymer films and a Ag/AgCl wire cathode coiled around the anode. Three different electropolymerized films prepared from m-phenylenediamine (m-PD), 2,3-diaminonaphthalene (2,3-DAN), and 5-amino-1-naphthol (5A1N) are compared in terms of their permselectivity for NO over major biological interferents such as anionic nitrite, ascorbic acid, uric acid; neutral acetaminophen; and cationic dopamine. Poly-5A1N film layer among the three different polymers shows the best anti-interference characteristics for all the electroactive interferents examined. Indeed, single polymer film of electropolymerized 5A1N without any additional modification as a NO selective membrane is confirmed to be sufficient to reject anionic, neutral, as well as cationic interferents while allowing relatively high permeation of NO through it. Other analytical performance of the NO microsensor fabricated with poly-5A1N is evaluated: reliable linear dynamic range (a few tens nM to mM); sensitivity of 122.0 AE 2.5 pA/mM; detection limit of < 5.8 nM (S/N ¼ 3); response time, t 90% < 5 s, which are excellent when considering the small sensor size. Another sensor design which has both an anode (poly-5A1N modified platinized Pt) and a cathode (Ag/AgCl disk) embedded in a single sensor body is also presented.

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“…Endothelial cell homeostasis is maintained largely through the synthesis of nitric oxide (NO), from the precursor L-arginine, under the influence of the enzyme nitric oxide synthase (eNOS) (17). NO serves several critical anti-inflammatory (9), anti-thrombotic (26), and anti-atherosclerotic (7) roles within blood vessels, in addition to promoting postnatal angiogenesis and reparative vasculogenesis (2).…”

mentioning

confidence: 99%

Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis

Lovren¹,

Pan²,

Shukla³

et al. 2009

American Journal of Physiology-Endocrinology and Metabolism

101

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-Improving endothelial nitric oxide synthase (eNOS) bioactivity and endothelial function is important to limit native, vein graft, and transplant atherosclerosis. Visfatin, a NAD biosynthetic enzyme, regulates the activity of the cellular survival factor, Sirt1. We hypothesized that visfatin may improve eNOS expression, endothelial function, and postnatal angiogenesis. In human umbilical vein (HUVEC) and coronary artery endothelial cells, we evaluated the effects of recombinant human visfatin on eNOS protein and transcript expression and mRNA stability, in the presence and absence of visfatin RNA silencing. We also assessed visfatin-induced protein kinase B (Akt) activation and its association with src-tyrosine kinases, phosphorylation of Ser 1177 within eNOS in the presence and absence of phosphatidylinositol 3-kinase (PI 3-kinase) inhibition with LY-294002, and evaluated the contributory role of extracellular signal-regulated kinase 1/2. Finally, we determined the impact of visfatin on HUVEC migration, proliferation, inflammation-induced permeability, and in vivo angiogenesis. Visfatin (100 ng/ml) upregulated and stabilized eNOS mRNA and increased the production of nitric oxide and cGMP. Visfatin-treated HUVEC demonstrated greater proliferation, migration, and capillary-like tube formation but less tumor necrosis factor-␣-induced permeability; these effects were decreased in visfatin gene-silenced cells. Visfatin increased total Akt and Ser 473 -phosphoAkt expression with concomitant rises in eNOS phosphorylation at Ser 1177 ; these effects were blocked by LY-2940002. Studies with PP2 showed that the nonreceptor tyrosine kinase, src, is an upstream stimulator of the PI 3-kinase-Akt pathway. Visfatin also activated mitogen-activated protein (MAP) kinase through PI 3-kinase, and mitogen/extracellular signal-regulated kinase inhibition attenuated visfatin-elicited Akt and eNOS phosphorylation. Visfatin-filled Matrigel implants showed an elevated number of infiltrating vessels, and visfatin treatment produced significant recovery of limb perfusion following hindlimb ischemia. These results indicate a novel effect of visfatin to stimulate eNOS expression and function in endothelial cells, via a common upstream, src-mediated signaling cascade, which leads to activation of Akt and MAP kinases. Visfatin represents a translational target to limit endothelial dysfunction, native, vein graft and transplant atherosclerosis, and improve postnatal angiogenesis. nitric oxide; mice; endothelium; atherosclerosis; visfatin; protein kinase B; phosphatidylinositol 3-kinase; mitogen-activated protein kinase; endothelial nitric oxide synthase

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Nitric Oxide Inhibition Enhances Platelet Aggregation in Experimental Anti-Thy-1 Nephritis

Cited by 15 publications

References 23 publications

Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease

Uncoupling of the VEGF-endothelial nitric oxide axis in diabetic nephropathy: an explanation for the paradoxical effects of VEGF in renal disease

Simple Fabrication of Amperometric Nitric Oxide Microsensors Based on Electropolymerized Membrane Films

Visfatin activates eNOS via Akt and MAP kinases and improves endothelial cell function and angiogenesis in vitro and in vivo: translational implications for atherosclerosis

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