The in vitro effects of niacin on platelet biomarkers in human volunteers

Serebruany, Victor L.; Malinin, Alex I.; Aradi, Dániel; Kuliczkowski, Wiktor; Norgard, Nicholas B; Boden, William E.

doi:10.1160/th10-01-0015

Cited by 18 publications

(6 citation statements)

References 35 publications

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“…While laropiprant at 1 µmol/L had no effect on thrombus formation, it caused a pronounced inhibition at 10 µmol/L, comparable to the inhibition of thrombogenesis by acetylsalicylic acid (1 mmol/L) (Figure 6). It has been shown that niacin and its metabolite niceritrol inhibit platelet aggregation in vitro [40], [41] and cause the release of TXA 2 , PGD 2 and PGE 2 at a clinically relevant concentration of 3 mmol/L [41]. Therefore, we investigated the effect of niacin on thrombus formation.…”

Section: Resultsmentioning

confidence: 99%

“…It has been shown that niacin and its metabolite niceritrol inhibit platelet aggregation in vitro [40], [41] and incubation of whole blood with niacin at a clinically relevant concentration increases the concentrations of PGD 2 , PGE 2 and TXA 2 [41]. Our results show that niacin causes a profound inhibition of thrombus formation in vitro ; however, prostaglandins such as PGD 2 do not seem to be involved in this process, since pre-treatment of blood with acetylsalicylic acid as well as laropiprant did not counteract this effect.…”

Section: Discussionmentioning

confidence: 99%

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Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation

et al. 2012

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The use of the lipid lowering agent niacin is hampered by a frequent flush response which is largely mediated by prostaglandin (PG) D2. Therefore, concomitant administration of the D-type prostanoid (DP) receptor antagonist laropiprant has been proposed to be a useful approach in preventing niacin-induced flush. However, antagonizing PGD2, which is a potent inhibitor of platelet aggregation, might pose the risk of atherothrombotic events in cardiovascular disease. In fact, we found that in vitro treatment of platelets with laropiprant prevented the inhibitory effects of PGD2 on platelet function, i.e. platelet aggregation, Ca2+ flux, P-selectin expression, activation of glycoprotein IIb/IIIa and thrombus formation. In contrast, laropiprant did not prevent the inhibitory effects of acetylsalicylic acid or niacin on thrombus formation. At higher concentrations, laropiprant by itself attenuated platelet activation induced by thromboxane (TP) and E-type prostanoid (EP)-3 receptor stimulation, as demonstrated in assays of platelet aggregation, Ca2+ flux, P-selectin expression, and activation of glycoprotein IIb/IIIa. Inhibition of platelet function exerted by EP4 or I-type prostanoid (IP) receptors was not affected by laropiprant. These in vitro data suggest that niacin/laropiprant for the treatment of dyslipidemias might have a beneficial profile with respect to platelet function and thrombotic events in vascular disease.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation

et al. 2012

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“…Since the increase of CD62p is not altered with time prolongation, it is considered the 'gold standard' of platelet activation markers ( 22 ). Therefore, we investigated the change of platelet function by detecting the expression of PAC-1, CD62p and CD42b ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Role of platelet function and platelet membrane glycoproteins in children with primary immune thrombocytopenia

Chen

Jing

Guo

et al. 2016

Molecular Medicine Reports

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The aim of the present study was to examine and understand changes in platelet functions prior to and after the treatment of primary immune thrombocytopenia (ITP) in children. An automatic hematology analyzer and whole blood flow cytometry were used to detect immature platelet fraction (IPF), IPC and membrane glycoproteins (CD62p, PAC-1 and CD42b) in ITP children (ITP group), children with complete response after ITP treatment (ITP-CR group) and children with elective surgery (normal control group). The results showed that, levels of platelet count (PLT) and plateletcrit in the ITP group were lower alhtough the levels of mean platelet volume, platelet distribution width and platelet-large cell ratio (P-LCR) were higher than those in the normal control and ITP-CR groups. PLT in the ITP-CR group was lower than that in the normal controls. Additionally, IPF% was higher in the normal control and ITP-CR groups, IPC was lower in the ITP group compared to the normal control and ITP-CR groups. Furthermore, prior to ADP activation, the expression levels of CD62p, PAC-1 and CD42b in the ITP group were lower in ITP group than those in the normal control and ITP-CR groups. The expression level of PAC-1 was lower in the ITP-CR and normal control groups. No differences were identified in CD62p and CD42b expression levels. Following ATP activation, CD62p, PAC-1 and CD42b expression in the ITP group was lower than that in the normal control and ITP-CR groups. PAC-1 expression was lower while CD62p expression was higher in the ITP-CR group compared to the normal control group. In conclusion, the activation of platelets in ITP children was low. Decreased platelet function, platelet parameters and platelet glycoproteins may be used as markers for monitoring the treatment efficacy in ITP children.

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“…In contrast, applying therapeutic strategies that modulate lipid levels and increase permeability and fluidity of cell membranes by altering lipid contents causes vascular benefit via diminished thrombotic occlusions. This appears to be true for statins [24], niacin [25], or fibrates [26]. There are multiple reports that PO-3A indeed impact platelet activity.…”

Section: Discussionmentioning

confidence: 99%

Early Impact of Prescription Omega-3 Fatty Acids on Platelet Biomarkers in Patients with Coronary Artery Disease and Hypertriglyceridemia

Serebruany¹,

Miller²,

Pokov³

et al. 2011

Cardiology

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Background: Prescription omega-3-acid ethyl esters (PO-3A) have been tested for outcome benefits in patients with coronary artery disease (CAD), arrhythmias and heart failure. Some evidence suggests that PO-3A may exert their benefit via inhibiting platelets. We tested the hypothesis that PO-3A may inhibit platelet activity in patients with documented stable CAD, beyond the antiplatelet properties of aspirin and statins. Methods: Thirty patients with documented CAD and triglycerides over 250 mg/dl treated with aspirin (70–160 mg/daily) and statins (simvastatin equivalence dose: 5–40 mg/daily) were randomized 1:1:1 to Omacor™ 1 g/day (DHA/EPA ratio 1.25:1.0), Omacor 2 g/day, or a placebo for 2 weeks. Platelet tests including aggregometry and flow cytometry and cartridge analyzer readings were performed at baseline and at 1 and 2 weeks following PO-3A therapy. Results: ADP-induced platelet aggregation (p = 0.037), GP IIb/IIIa antigen (p = 0.031) and activity (p = 0.024), and P-selectin (p = 0.041) were significantly reduced after PO-3A, while platelet/endothelial cell adhesion molecule (p = 0.09), vitronectin receptor (p = 0.16), formation of platelet-monocyte microparticles (p = 0.19) and the VerifyNow IIb/IIIa test (p = 0.27) only exhibited nonsignificant trends suggestive of reduced platelet activity. Finally, collagen- and arachidonic acid-induced aggregation, closure time with the PFA-100 device and expression of thrombospondin (CD36), GP Ib (CD42b), LAMP-3 (CD63), LAMP-1 (CD107a), CD40-ligand (CD154), GP37 (CD165), and PAR-1 receptor intact (SPAN 12) and cleaved (WEDE-15) epitopes were not affected by 2 weeks of PO-3A. Conclusion: Independently of the dose and already at 1 week, short-term therapy with PO-3A provided a modest reduction of platelet activity biomarkers, despite concomitant aspirin and statin therapy, when compared to a placebo. The effect of PO-3A is unique, differs from other known antiplatelet agents and suggests potential pleiotropism. These preliminary randomized data call for confirmation in prospective studies.

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The in vitro effects of niacin on platelet biomarkers in human volunteers

Cited by 18 publications

References 35 publications

Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation

Laropiprant Attenuates EP3 and TP Prostanoid Receptor-Mediated Thrombus Formation

Role of platelet function and platelet membrane glycoproteins in children with primary immune thrombocytopenia

Early Impact of Prescription Omega-3 Fatty Acids on Platelet Biomarkers in Patients with Coronary Artery Disease and Hypertriglyceridemia

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