Platelet activation in normo- and hyperlipoproteinemias

Nimpf, Johannes; Wurm, H.; Kostner, Gerhard M.; Kenner, Th.

doi:10.1007/bf01907750

Cited by 26 publications

(6 citation statements)

References 163 publications

(92 reference statements)

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“…It has been reported that circulating activated platelets and increased thrombotic risk are related to many cardiovascular events such as angioplasty, stroke, diabetes mellitus, and hyperlipidemia [31][32][33][34]. In the present study, using a flow cytometric method, we found that both P-selectin and fibrinogen expressions on the surface of platelets were significantly higher in the hyperlipidemic group compared to the healthy group.…”

Section: Discussionsupporting

confidence: 56%

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

Özsavcı¹,

Şener²,

Oba³

et al. 2010

Turk J Hematol

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Objective: We aimed to detect novel in vitro effects of clopidogrel on platelets by assessment of the following parameters: malondialdehyde, glutathione, nitrite, aggregation response, and expressions of P-selectin, fibrinogen, apolipoprotein A1, apolipoprotein B, and phosphatidylserine. Materials and Methods: Platelets were obtained from healthy (n: 9) and hyperlipidemic (n: 9) volunteers. Expressions of P-selectin, fibrinogen, apolipoproteins A1/B and phosphatidylserine with and without clopidogrel were assayed by flow cytometry. Malondialdehyde, glutathione, aggregation and nitrite levels were also assayed. Results: Without clopidogrel, the baseline values of platelet aggregation, malondialdehyde, and expressions of P-selectin, fibrinogen and phosphatidylserine were significantly higher, whereas nitrite and expression of apolipoproteins A1/B were significantly lower in hyperlipidemics than in the healthy group. In both groups, clopidogrel significantly reduced aggregation and expression of fibrinogen, but it elevated nitrite levels. Clopidogrel significantly decreased P-selectin and phosphatidylserine expression and malondialdehyde but increased expressions of apolipoproteins A1/B only in hyperlipidemics. Conclusion: It seems that clopidogrel has some new in vitro antiplatelet effects. The present study is a basic in vitro study to suggest new insights into the effects of clopidogrel on platelet functions. Özet Amaç: Klopidogrelin trombositler üzerinde yeni in vitro etkilerini tayin etmek: Malondialdehit, glutatyon, nitrit, aggregasyon cevabı, P-selektin, fibrinojen, apolipoprotein A1, apolipoprotein B ve fosfatidilserin ekspresyonları. Yöntem ve Gereçler: Sağlıklı (n: 9) ve hiperlipidemik (n: 9) olgulardan trombositler elde edildi. Klopidogrelli ve klopidogrelsiz trombositlerde P-selektin, fibrinojen, apolipoprotein A1, apolipoprotein B ve fosfatidilserin ekspresyonları flow sitometre ile tayin edildi. Malondialdehit, glutatyon, aggregasyon ve nitrit seviyeleri de tayin edildi. Bulgular: Klopidogrel yokluğunda, hiperlipidemililerde kontrollere göre trombosit agregasyonu, malondialdehit, P-Selektin, fibrinojen ve fosfatidilserin ekspresyonunun başlangıç değerleri yüksek; bununla birlikte nitrit, apolipoprotein A1 ve apolipoprotein B ekspresyonlarınınki ise daha düşüktü. Her iki grupta, klopidogrel anlamlı düzeyde aggregasyonu ve fibrinojen ekspresyonunu azalttı, fakat nitrit seviyelerini artırdı. Klopidogrel sadece hiperlipidemililerde P-selektin ve fosfatidilserin ekspresyonunu ve malondialdehiti azalttı ancak apolipoprotein A1 ve apolipoprotein B ekspresyonlarını artırdı.

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Section: Discussionsupporting

confidence: 56%

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

Özsavcı¹,

Şener²,

Oba³

et al. 2010

Turk J Hematol

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“…The flow activity in the aneurysm depends on the flow rate and on the geometry. Low flow velocity is one of the conditions for the initiation of blood coagulation within an aneurysm (5). It can be assumed that blood clots may be generated within the central whirl of the aneurysm.…”

Section: Resultsmentioning

confidence: 99%

Numerical blood flow analysis: Arterial bifurcation with a saccular aneurysm

et al. 1988

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The flow pattern and the paths of fluid particles in a saccular aneurysm located at the bifurcation of an intracranial arterial segment are investigated with a numerical method. A normal physiological flow pattern was assumed as input to the studied segment. The theoretical study is carried out for two different Reynolds numbers and two different geometries of the aneurysm. The governing equations for incompressible Newtonian fluid flow are solved using the finite element method. The results show the disturbed blood flow in the pathologically altered bifurcation and the flow activity in the aneurysms. It is particularly important that blood particles can circulate in a whirl within the aneurysm for a time which seems long enough to permit the generation of cell aggregates or/and blood clots.

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“…6 Previous reports described increased platelet activation in disease states with impaired NO bioavailability such as acute coronary syndromes, 7 heart failure, 8 diabetes, 9 and hypercholesterolemia. 10 However, the direct relationship between NO bioavailability and platelet activation in humans remains unclear.…”

mentioning

confidence: 99%

Rapid Regulation of Platelet Activation In Vivo by Nitric Oxide

et al. 2004

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Background-Platelet activation is a feature of many cardiovascular diseases characterized by endothelial dysfunction.The mechanistic relationship between impaired systemic nitric oxide (NO) bioavailability and platelet activation in vivo remains unclear. We investigated whether acute inhibition of NO production in humans modulates platelet activation in vivo and whether exogenous NO would counteract such an effect. Methods and Results-Intravenous injection of the NO synthase inhibitor N G -monomethyl-L-arginine in healthy volunteers resulted in NO synthase inhibition as detected by increased blood pressure and by significantly reduced phosphorylation of platelet vasodilator-stimulated phosphoprotein, an indicator of NO signaling. NO synthase inhibition increased platelet activation as determined by enhanced platelet binding of fibrinogen and surface expression of P-selectin, glycoprotein 53, and CD40 ligand, demonstrating tonic inhibition of platelet activation by NO production in vivo. Sublingual administration of the NO donor glyceryl trinitrate normalized platelet VASP phosphorylation and restored markers of platelet activation to baseline levels. Conclusions-Acute inhibition of endogenous NO production in humans causes rapid platelet activation in vivo, which is reversed by exogenous NO, demonstrating that platelet function in vivo is rapidly regulated by NO bioavailability. Key Words: glycoproteins Ⅲ nitric oxide Ⅲ P-selectin Ⅲ phosphoproteins Ⅲ platelets N itric oxide (NO), generated by NO synthase (NOS), inhibits platelet activation 1 as demonstrated by in vitro experiments such as inhibition of platelet aggregation by endothelial cells 2 or NO donors. 3,4 NO can even reverse agonist-induced activation of glycoprotein IIb/IIIa. 5 Chronic inhibition of NO formation in animal models is associated with impaired fibrinolysis and enhanced thrombin and tissue factor generation. 6 Previous reports described increased platelet activation in disease states with impaired NO bioavailability such as acute coronary syndromes, 7 heart failure, 8 diabetes, 9 and hypercholesterolemia. 10 However, the direct relationship between NO bioavailability and platelet activation in humans remains unclear.NO-dependent phosphorylation of vasodilator-stimulated phosphoprotein (VASP) is an essential regulatory component in the inhibition of platelet activation and correlates with inhibition of fibrinogen binding to glycoprotein IIb/IIIa, 11,12 P-selectin expression, and platelet adhesion. 13 With specific antibodies, VASP phosphorylation provides a sensitive monitor of defective NO/cGMP signaling, and reduced NO bioavailability in several pathophysiological states correlates with reduced VASP phosphorylation. 14 In the present study, we investigated whether acute changes in NO bioavailability in healthy human volunteers would affect platelet activation as determined by activity of the fibrinogen receptor and platelet degranulation. MethodsVenous blood was taken from 12 healthy nonsmoking male donors (age, 29Ϯ1.3 years) resting in a s...

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Platelet activation in normo- and hyperlipoproteinemias

Cited by 26 publications

References 163 publications

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

New in vitro effects of clopidogrel on platelets in hyperlipidemic and healthy subjects

Numerical blood flow analysis: Arterial bifurcation with a saccular aneurysm

Rapid Regulation of Platelet Activation In Vivo by Nitric Oxide

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