Cooperation between Aspirin-Triggered Lipoxin and Nitric Oxide (NO) Mediates Antiadhesive Properties of 2-(Acetyloxy)benzoic Acid 3-(Nitrooxymethyl)phenyl Ester (NCX-4016) (NO-Aspirin) on Neutrophil-Endothelial Cell Adherence

2004 ◽  
Vol 309 (3) ◽  
pp. 1174-1182 ◽  
Author(s):  
Stefano Fiorucci ◽  
Eleonora Distrutti ◽  
Andrea Mencarelli ◽  
Giovanni Rizzo ◽  
Anna Rita Di Lorenzo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Benzoic Acid ◽  
Phenyl Ester ◽  
Cell Adherence ◽  
Ncx 4016

scholarly journals Roles of platelet and endothelial cell COX-1 in hypercholesterolemia-induced microvascular dysfunction

2007 ◽  
Vol 293 (6) ◽  
pp. H3636-H3642 ◽  
Author(s):  
Anitaben Tailor ◽  
Katherine C. Wood ◽  
John L. Wallace ◽  
Robert D. Specian ◽  
D. Neil Granger
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Platelet Adhesion ◽  
Microvascular Dysfunction ◽  
Patients At Risk ◽  
Microvascular Inflammation ◽  
Nitric Oxide Releasing ◽  
Adhesion Of Platelets ◽  
Ncx 4016 ◽  
Cox 1

Aspirin is a common preventative therapy in patients at risk for cardiovascular diseases, yet little is known about how aspirin protects the vasculature in hypercholesterolemia. The present study determines whether aspirin, nitric oxide-releasing aspirin (NCX-4016), a selective cyclooxygenase (COX)-1 inhibitor (SC560), or genetic deficiency of COX-1 prevents the inflammatory and prothrombogenic phenotype assumed by hypercholesterolemic (HC) venules. Aspirin or NCX-4016 (60 mg/kg) was administered orally for the last week of a 2-wk HC diet. COX-1-deficient (COX-1−/−) and wild-type (WT) mice were transplanted with WT (WT/COX-1−/−) or COX-1−/−(COX-1−/−/WT) bone marrow, respectively. HC-induced adhesion of platelets and leukocytes in murine intestinal venules, observed with intravital fluorescence microscopy, was greatly attenuated in aspirin-treated mice. Adhesion of aspirin-treated platelets in HC venules was comparable to untreated platelets, whereas adhesion of SC560-treated platelets was significantly attenuated. HC-induced leukocyte and platelet adhesion in COX-1−/−/WT chimeras was comparable to that in SC560-treated mice, whereas the largest reductions in blood cell adhesion were in WT/COX-1−/−chimeras. NCX-4016 treatment of platelet recipients or donors attenuated leukocyte and platelet adhesion independent of platelet COX-1 inhibition. Platelet- and endothelial cell-associated COX-1 promote microvascular inflammation and thrombogenesis during hypercholesterolemia, yet nitric oxide-releasing aspirin directly inhibits platelets independent of COX-1.

Prevention by NCX 4016, a nitric oxide-donating aspirin, but not by aspirin, of the acute endothelial dysfunction induced by exercise in patients with intermittent claudication

2007 ◽  
Vol 97 (03) ◽  
pp. 444-450 ◽  
Author(s):  
Rino Migliacci ◽  
Alessandra Procacci ◽  
Paola De Monte ◽  
Erminio Bonizzoni ◽  
Paolo Gresele
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Intermittent Claudication ◽  
Treadmill Exercise ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Lower Limbs ◽  
Exercise Induced ◽  
Induced Changes ◽  
Ncx 4016

SummaryIschemia/reperfusion damage evokes systemic inflammation and endothelial dysfunction in patients with intermittent claudication. We compared the effects of aspirin with those of a nitric oxide-donating aspirin in preventing the acute, systemic endothelial dysfunction provoked by exercise-induced ischemia of the lower limbs in patients with intermittent claudication. In a prospective, randomized, single-blind, parallel-groups trial among 44 patients with intermittent claudication we compared four weeks of aspirin (100 mg o.d.) with NCX 4016 (800 mg b.i.d.). Primary end point was the exercise-induced changes in brachial flow-mediated vasodilation (FMD) at day 28; secondary end points were effort-induced changes of markers of neutrophil (plasma elastase) and endothelial (soluble VCAM-1) activation. Baseline FMD was comparable in the two groups, both on day I (pre-treatment: aspirin = 3.1 ± 0.5%, nitroaspirin = 3.9 ± 0.7%, p=NS), and on day 28 (aspirin = 3.4 ± 0.7%, NCX 4016 = 3.2 ± 0.6%, p=NS). Maximal treadmill exercise induced an acute worsening of FMD in both groups at baseline (aspirin = –1.15%, nitroaspirin = –1.76%); after four weeks treatment, the impairment of FMD induced by exercise was still present in the aspirin-treated group (- 1.46%) while it was abolished in the NCX 4016-treated group (+ 0.79%, p= 0.038 vs. aspirin). Similarly, exercise induced an increase of plasma elastase and of sVCAM-l which were not affected by aspirin while they were suppressed by NCX 4016. Maximal treadmill exercise induces a systemic arterial endothelial dysfunction in patients with intermittent claudication. A nitric oxide-donating aspirin, but not aspirin, prevents effort-induced endothelial dysfunction.

Effects of lipoproteins from pre-eclamptic women on umbilical endothelial cell 6-oxo-prostaglandin F1α and endothelin 1 synthesis, and nitric oxide synthase 3 mRNA expression

1999 ◽  
Vol 97 (6) ◽  
pp. 697-706 ◽  
Author(s):  
A. BARDEN ◽  
L. J. BEILIN ◽  
K. BOTH ◽  
J. RITCHIE ◽  
P. LEEDMAN ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Pregnant Women ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Endothelin 1 ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase

In order to evaluate whether lipid abnormalities may contribute to endothelial dysfunction in pre-eclampsia, the present study examined the in vitro effects of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), isolated from women with pre-eclampsia and matched controls, on the endothelial synthesis of 6-oxo-prostaglandin F1α (6-oxo-PGF1α; a metabolite of prostacyclin) and endothelin 1, and on the expression of nitric oxide synthase 3 (NOS3) mRNA. VLDL, LDL and HDL cholesterol were isolated from 20 pre-eclamptic and 20 age- and gestation-matched normal pregnant women. The lipoproteins (50 μg/ml) and lipoprotein-free control plasma were incubated for 1, 3 and 6 h at 37 °C with a human umbilical endothelial cell line. The synthesis of 6-oxo-PGF1α and endothelin 1, and NOS3 mRNA expression, were measured at each time point. VLDL from pre-eclamptic women stimulated endothelial cell 6-oxo-PGF1α synthesis to a lesser extent than that from normal pregnant women (P< 0.05). LDL from women with pre-eclampsia also stimulated 6-oxo-PGF1α synthesis to a lesser extent than LDL from normal pregnant women, but the effect was less sustained. The effect of HDL from women with pre-eclampsia on 6-oxo-PGF1α synthesis was similar to that of HDL from normal pregnant women. The pre-incubation levels of lipid peroxides in VLDL and LDL were not different between the normal pregnant and pre-eclamptic women, and cannot account for the decrease in 6-oxo-PGF1α synthesis. VLDL, LDL and HDL from women with pre-eclampsia did not affect endothelial cell synthesis of endothelin 1 or expression of NOS3 mRNA differently from lipoproteins from normal pregnant women. This study suggests that VLDL, and to a lesser extent LDL, from women with pre-eclampsia could potentially contribute to the reduced systemic 6-oxo-PGF1α synthesis observed in the pre-eclamptic syndrome.

The smoking-associated oxidant hypothiocyanous acid induces endothelial nitric oxide synthase dysfunction

2013 ◽  
Vol 457 (1) ◽  
pp. 89-97 ◽  
Author(s):  
Jihan Talib ◽  
Jair Kwan ◽  
Aldwin Suryo Rahmanto ◽  
Paul K. Witting ◽  
Michael J. Davies
Keyword(s):  
Nitric Oxide ◽  
Enzyme Activity ◽  
Endothelial Cell ◽  
Nitric Oxide Synthase ◽  
Endothelial Nitric Oxide Synthase ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Monomer Form

The smoking-associated oxidant hypothiocyanous acid converts active dimeric endothelial cell nitric oxide synthase into its monomer form, decreases enzyme activity and releases Zn2+. This is ascribed to targeting of the critical Zn2+–thiol cluster by this thiol-specific oxidant.

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