Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

Virgolini, Irene; Li, S; Borggrefe, Martin; Koller, Elisabeth; Angelberger, P.; Sinzinger, H.

doi:10.1161/01.atv.12.7.849

Cited by 15 publications

(10 citation statements)

References 42 publications

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“…One of the platelet abnormalities, observed in the hyperlipidemic group, is the change in membrane receptor responses. It has been shown that patients with atherosclerosis, diabetes and hyperlipidemia have significantly lower platelet LDL and HDL binding sites [7,8,41]. In our study, expressions of both apo B (also LDL) and apo A (also HDL) on platelets were lower in the hyperlipidemic patients.…”

Section: Discussionsupporting

confidence: 50%

“…There is some evidence of these lipoproteins interacting with platelets via specific receptors. It has been reported that there are high-density lipoprotein (HDL) and LDL binding sites on platelets, and those binding sites are reduced in familial hyperlipidemia [7,8]. In our previous study, we had detected that apolipoprotein-A1 (anti-apo-A1) was able to bind to the platelet surface indicating the presence of apo-A1 binding sites on platelets by a flow cytometric method [9].…”

Section: Introductionmentioning

confidence: 94%

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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: 50%

Section: Introductionmentioning

confidence: 94%

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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Section: 10mentioning

confidence: 99%

“…HDL 3 , the major HDL subfraction in blood, is known to interact with specific binding sites on platelets that appear to be identical with GP IIb/IIIa. [11][12][13][14] In human platelets, HDL 3 was also shown to activate cellular phospholipases, resulting in the formation of DAG. [15][16][17][18] The involvement of both phosphatidylcholine-specific phospholipase C and phosphatidylcholine-specific phospholipase D was postulated.…”

mentioning

confidence: 99%

HDL₃-Mediated Inhibition of Thrombin-Induced Platelet Aggregation and Fibrinogen Binding Occurs via Decreased Production of Phosphoinositide-Derived Second Messengers 1,2-Diacylglycerol and Inositol 1,4,5-tris-Phosphate

Nofer

Walter

Kehrel

et al. 1998

ATVB

131

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Abstract-We demonstrate that physiological concentrations of HDL 3 inhibit the thrombin-induced platelet fibrinogen binding and aggregation in a time-and concentration-dependent fashion. The underlying mechanism includes HDL 3 -mediated inhibition of phosphatidylinositol 4,5-bis-phosphate turnover, 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate formation, and intracellular calcium mobilization. The inhibitory effects of HDL 3 on inositol 1,4,5-tris-phosphate formation and intracellular calcium mobilization were abolished after covalent modification of HDL 3 with dimethylsuberimidate. Furthermore, they could be blocked by calphostin C and bis-indolylmaleimide, 2 highly selective and structurally unrelated protein kinase C inhibitors. However, the inhibitory effects of HDL 3 were not blocked by H89, a protein kinase A inhibitor. In addition, HDL 3 failed to induce cAMP formation but stimulated the phosphorylation of the protein kinase C 40-to 47-kD major protein substrate. We observed a close temporal relationship between the HDL 3 -mediated inhibition of thrombininduced inositol 1,4,5-tris-phosphate formation, intracellular calcium mobilization, and fibrinogen binding and the phosphorylation of the protein kinase C 40-to 47-kD major protein substrate. Taken together, these findings indicate that the HDL 3 -mediated inhibition of thrombin-induced fibrinogen binding and aggregation occurs via inhibition of phosphatidylinositol 4,5-bis-phosphate turnover and formation of 1,2-diacylglycerol and inositol 1,4,5-tris-phosphate. Protein kinase C may be involved in this process. (Arterioscler Thromb Vasc Biol. 1998;18:861-869.)Key Words: high-density lipoprotein Ⅲ protein kinase C Ⅲ signal transduction Ⅲ platelet aggregation Ⅲ fibrinogen B oth HDL and platelets are intimately involved in the pathogenesis of atherosclerosis, thrombosis, and coronary heart disease.1-3 Numerous observations demonstrated a direct effect of HDL on platelet functions.4 Platelet hyperreactivity was noted in subjects with hypoalphalipoproteinemia.5 Decreased activation of platelets by strong agonists such as thrombin and collagen has been reported in the presence of physiological concentrations of HDL.6-8 Furthermore, HDL inhibited thromboxane A 2 liberation, and addition of HDL to clotting blood diminished platelet thromboxane A 2 formation capacity. 9,10The mechanism underlying the effects of HDL on platelet function is little understood. HDL 3 , the major HDL subfraction in blood, is known to interact with specific binding sites on platelets that appear to be identical with GP IIb/IIIa. [11][12][13][14] In human platelets, HDL 3 was also shown to activate cellular phospholipases, resulting in the formation of DAG.15-18 The involvement of both phosphatidylcholine-specific phospholipase C and phosphatidylcholine-specific phospholipase D was postulated. 16 -18 Recently, the PKC-dependent enhancement of the Na ϩ /H ϩ antiport in the presence of HDL 3 has been reported. 19Both HDL 3 -induced DAG formation and Na ϩ /H ϩ exchange stimulation w...

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“…More recent studies have shown that [ 99m Tc]-NGA, in combination with another receptor tracer, [ 123 I]-Tyr-A-14-insulin, can be successfully applied to differentiate malignant from benign liver lesions [4]. Another field of 'receptor nuclear medicine' is the application of radiolabelled autologous lipoproteins in arteriosclerosis to study the functional aspects of arteriosclerotic plaque formation [5], influences of lipid-lowering therapy [6] and, more recently, the role of modified LDL [7]. The possible application of radiolabelled VEGF (vascular endothelial growth factor) for imaging the endothelium [8] and of a synthetic apolipoprotein fragment, [ 99m Tc]-SP-4, for studying atherosclerotic plaques [9] has also been outlined.…”

Section: Introductionmentioning

confidence: 99%

Mack Forster Award Lecture Receptor nuclear medicine: vasointestinal peptide and somatostatin receptor scintigraphy for diagnosis and treatment of tumour patients

Virgolini

1997

Eur J Clin Investigation

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Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

Cited by 15 publications

References 42 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

HDL₃-Mediated Inhibition of Thrombin-Induced Platelet Aggregation and Fibrinogen Binding Occurs via Decreased Production of Phosphoinositide-Derived Second Messengers 1,2-Diacylglycerol and Inositol 1,4,5-tris-Phosphate

Mack Forster Award Lecture Receptor nuclear medicine: vasointestinal peptide and somatostatin receptor scintigraphy for diagnosis and treatment of tumour patients

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Binding of 111In-labeled HDL to platelets from normolipemic volunteers and patients with heterozygous familial hypercholesterolemia.

Cited by 15 publications

References 42 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

HDL3-Mediated Inhibition of Thrombin-Induced Platelet Aggregation and Fibrinogen Binding Occurs via Decreased Production of Phosphoinositide-Derived Second Messengers 1,2-Diacylglycerol and Inositol 1,4,5-tris-Phosphate

Mack Forster Award Lecture Receptor nuclear medicine: vasointestinal peptide and somatostatin receptor scintigraphy for diagnosis and treatment of tumour patients

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Product

Resources

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HDL₃-Mediated Inhibition of Thrombin-Induced Platelet Aggregation and Fibrinogen Binding Occurs via Decreased Production of Phosphoinositide-Derived Second Messengers 1,2-Diacylglycerol and Inositol 1,4,5-tris-Phosphate