scholarly journals The aptamer ARC1779 is a potent and specific inhibitor of von Willebrand Factor-mediated ex vivo platelet function in ST-elevation and non-ST-elevation acute myocardial infarction

2008 ◽  
Vol 8 (Suppl 1) ◽  
pp. A54
Author(s):  
Alexander O Spiel ◽  
Florian B Mayr ◽  
Nathalie Ladani ◽  
Patricia G Merlino ◽  
Robert Schaub ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Ex Vivo ◽  
Specific Inhibitor ◽  
St Elevation ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Elevation Acute Myocardial Infarction

The aptamer ARC1779 is a potent and specific inhibitor of von willebrand factor mediatedex vivoplatelet function in acute myocardial infarction

Platelets ◽  
2009 ◽  
Vol 20 (5) ◽  
pp. 334-340 ◽  
Author(s):  
Alexander O. Spiel ◽  
Florian B. Mayr ◽  
Nathalie Ladani ◽  
Patricia G. Wagner ◽  
Robert G. Schaub ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Von Willebrand Factor ◽  
Specific Inhibitor ◽  
Von Willebrand ◽  
Willebrand Factor

Unique Antiplatelet Effects of a Novel S-Nitrosoderivative of a Recombinant Fragment of von Willebrand Factor, AR545C: In Vitro and Ex Vivo Inhibition of Platelet Function

Blood ◽  
1999 ◽  
Vol 94 (5) ◽  
pp. 1693-1700
Author(s):  
Aida Inbal ◽  
Osnat Gurevitz ◽  
Ilia Tamarin ◽  
Regina Eskaraev ◽  
Angela Chetrit ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Platelet Aggregation ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Aggregate Formation ◽  
Recombinant Fragment ◽  
Von Willebrand ◽  
Willebrand Factor

The recombinant fragment of von Willebrand factor (vWF) spanning Ala444 to Asp730 and containing an Arg545Cys mutation (denoted AR545C) has antithrombotic properties that are principally a consequence of its ability to inhibit platelet adhesion to subendothelial matrix. Endothelial-derived nitric oxide (NO) can also inhibit platelet function, both as a consequence of inhibiting adhesion as well as activation and aggregation. Nitric oxide can react with thiol functional groups in the presence of oxygen to form S-nitrosothiols, which are naturally occurring NO derivatives that prolong the biological actions of NO. Because AR545C has a single free cysteine (Cys545), we attempted to synthesize the S-nitroso-derivative of AR545C and to characterize its antiplatelet effects. We successfully synthesized S-nitroso-AR545C and found that it contained 0.96 mol S-NO per mole peptide. S-nitroso-AR545C was approximately 5-fold more potent at inhibiting platelet agglutination than was the unmodified peptide (IC50 = 0.02 ± 0.006 μmol/L v 0.1 ± 0.03 μmol/L, P = .001). In addition and by contrast, S-nitroso-AR545C was a powerful inhibitor of adenosine diphosphate–induced platelet aggregation (IC50 = 0.018 ± 0.002 μmol/L), while AR545C had no effect on aggregation. These effects were confirmed in studies of adhesion to and aggregation on extracellular matrix under conditions of shear stress in a cone-plate viscometer, where 1.5 μmol/L S-nitroso-AR545C inhibited platelet adhesion by 83% and essentially completely inhibited aggregate formation, while the same concentration of AR545C inhibited platelet adhesion by 74% and had significantly lesser effect on aggregate formation on matrix (P ≤ .004 for each parameter by ANOVA). In an ex vivo rabbit model, we also found that S-nitroso-AR545C had a more marked and more durable inhibitory effect on botrocetin-induced platelet aggregation than did AR545C, and these differences were also reflected in the extent and duration of effect on the prolongation of the bleeding time in these animals. These data show that S-nitroso-AR545C has significant and unique antiplatelet effects, inhibiting both adhesion and aggregation, by blocking platelet GPIb receptor through the AR545C moiety and elevating platelet cyclic 3′,5′-guanosine monophosphate through the -SNO moiety. These observations suggest that this NO-modified fragment of vWF may have potential therapeutic benefits as a unique antithrombotic agent.

Von Willebrand Factor, Plasminogen Activator Inhibitor-1 and C-Reactive Protein Are Markers of Thrombolytic Efficacy in Acute Myocardial Infarction

1992 ◽  
Vol 68 (06) ◽  
pp. 678-682 ◽  
Author(s):  
F Andreotti ◽  
D R Hackett ◽  
A W Haider ◽  
M C Roncaglioni ◽  
G J Davies ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Plasminogen Activator ◽  
Von Willebrand Factor ◽  
Plasminogen Activator Inhibitor ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Activator Inhibitor

SummaryPlasma von Willebrand factor, plasminogen activator inhibitor activity and C-reactive protein were assessed as markers of coronary recanalisation in 30 patients with acute myocardial infarction receiving tissue-type plasminogen activator (t-PA). Blood samples were taken before t-PA (time 0), 4-hourly for 24 h and daily up to 72 h. A continuous electrocardiogram was recorded in the first 24 h. Coronary arteriography was performed 90 min and 24 h after the start of t-PA. Patients with a patent infarct artery (n = 17), compared to those with occluded artery (n = 13), showed a fall in von Willebrand factor from 0 to 24 h (p = 0.001), a greater fall in plasminogen activator inhibitor from 24 to 48 h (p = 0.04) and a fall in C-reactive protein from 48 to 72 h (p = 0.002). The accuracy of these indices compared favourably with time to peak plasma MB creatine kinase and ≥ 50% resolution of maximal ST-deviation on the electrocardiogram.Thus, changes in plasma von Willebrand factor, plasminogen activator inhibitor and C-reactive protein during the first 3 days of myocardial infarction are indicative of thrombolytic efficacy. Their concordant behaviour may reflect a common regulatory mechanism.

Abstract 3140: A Variant in the von Willebrand Factor Gene is Associated with Differences in Circulating Protein Levels and Platelet Function

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Dhananjay Vaidya ◽  
J E Herrera-Galeano ◽  
Lisa R Yanek ◽  
Taryn F Moy ◽  
Nauder Faraday ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Platelet Function ◽  
Von Willebrand Factor ◽  
Ex Vivo ◽  
Missense Variant ◽  
Minor Allele ◽  
Von Willebrand ◽  
Induced Aggregation ◽  
Willebrand Factor

Platelets are recruited to the site of vascular injury by von Willebrand factor (vWF) immobilized on exposed collagen. High circulating vWF levels are associated with myocardial infarction, while low levels are seen in the bleeding disorder von Willebrand’s disease (VWD). We examined the association of single nucleotide polymorphisms (SNPs) in the vWF gene with circulating vWF levels and with collagen-induced aggregation of ex vivo platelets in plasma. We genotyped 51 SNPs (with minor allele frequency >5%, constituting 25 linkage disequilibrium blocks) in the vWF gene in 2077 apparently healthy individuals with a family history of coronary disease (40% Black, 58% female), measured serum vWF levels, and ex vivo platelet aggregation to 10 mM collagen using optical aggregometry. Family-based additive genetic associations for age and sex adjusted vWF levels were assessed using the SAGE software package. Combined p-values for race-stratified analyses using meta-analysis were considered significant at p=0.002 (Bonferroni-corrected). Effect sizes were estimated using generalized estimating equations regression accounting for family structure. SNP rs216321 encoding the missense variant Q852R (minor allele frequency Whites 8%, Blacks 6%) was associated with vWF levels (p=0.003 [Whites], 0.077[Blacks], 0.002 [combined]). The variant Q852R neighbors a known VWD locus (R854Q). Each copy of Q852R was additively associated with a 13% lower level of vWF (adjusted for age, sex, and race, p=0.0003). However, this variant was recessive in association with collagen-induced aggregation, which was profoundly lower by 23% in minor allele homozygotes as compared to the other two genotypes (p=0.000004). We have discovered a novel association of a missense variant in the vWF gene with vWF blood levels and vWF-mediated platelet function. Whether this variant is adaptive (protecting from cardiovascular disease) or maladaptive (promoting inappropriate bleeding) remains to be determined.

scholarly journals Plasma von Willebrand factor level is transiently elevated in a rat model of acute myocardial infarction

2015 ◽  
Vol 10 (5) ◽  
pp. 1743-1749 ◽  
Author(s):  
YAN LI ◽  
LIQUN LI ◽  
FENGYUN DONG ◽  
LING GUO ◽  
YINGLONG HOU ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Von Willebrand Factor ◽  
Rat Model ◽  
Factor Level ◽  
Von Willebrand ◽  
Willebrand Factor
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