Platelet-Vessel Wall Interactions In Experimentally Induced Hypercholesterolemia

1981 ◽  
Author(s):  
E Tremoli ◽  
E Aqradi ◽  
A Socini ◽  
A Petroni ◽  
C Galli
Keyword(s):  
Platelet Aggregation ◽  
Vessel Wall ◽  
Aortic Wall ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Lower Sensitivity ◽  
High Cholesterol ◽  
Simple Method ◽  
Wall Interaction ◽  
Wall Interactions

A simple method was developed to study platelet-vesseln wall interactions based on the perfusion of platelet rich plasma (PRP) through isolated segments obtained from the aorta of the same animal. The inhibition of aggregation of the perfused PRP, indicating prostacyclin (PGI2)-like material production by aortic wall, was quantified. The effect was not present when normal PRP was perfused through the vessels obtained from aspirin-treated animals. This experimental model was used in the study of platelet-vessel wall interaction in normal (N) and hypercholesterolemic (HC) rabbits (one month on a high cholesterol -2% W/W - diet).In the HC animals increased aggregating response coupled with reduced platelet sensitivity to the inhibitory effect of exogenous PGI2 was observed. When PRP of the two groups of animals was perfused through their own aortas, the inhibition of aggregation was significantly lower in HC samples, suggesting ever lower aortic production or lower sensitivity to the inhibitory effect of PGI2-like material in treated animals. In addition a lower inhibition of platelet aggregation occurred after perfusion of PRP from HC animals through aortas of N rabbits, indicating a decreased platelet sensitivity to the inhibitory effect of PGI2-like material released.It appears that in experimental HC rabbits, platelet aggregation and their sensitivity to the antiaggregatory effect of PGI2 are significantly affected. In our experimen tal conditions, production of PGI2-like material in the aorta is not reduced, but the overall outcome of plateletvessel wall interaction is a reduced inhibition of platelet aggregatory response.

Effect of Sulphinpyrazone (SP) Aspirin (ASA) and Dipyridamole (DP) on Plateletvessel Wall Interaction after Oral Administration to Rabbits

1979 ◽  
Author(s):  
J.A. Davies ◽  
V.C. Menys
Keyword(s):  
Clinical Trials ◽  
Platelet Aggregation ◽  
Vessel Wall ◽  
Platelet Adhesion ◽  
Ex Vivo ◽  
Inhibitory Effect ◽  
Inhibitory Effects ◽  
Human Dose ◽  
Wall Interaction ◽  
Adhesion Of Platelets

Clinical trials of anti-platelet drugs have suggested that they may be useful in the prevention of thrombotic disease. While such drugs inhibit platelet function, those which act on cyclooxygenase also reduce PGI2 synthesis and may interfere with tne natural antithrombotic properties of the vessel wall. We studied the effects of SP, ASA and OP ex vivo on the platelet-vessel wall interaction. Rabbits were dosed by mouth with drug (at about twice the weight-adjusted human dose) or placebo for 5 days, then exsanguinated and aortas removed. Washed platelets prepared from the blood were labelled with 51Cr. and their adhesion to everted aortapr epared from treated or control rabbits was measured in a perfusion device. PGI2-like activity in aortic rings was assayed by its inhibitory effect on platelet aggregation to ADP. Adhesion of platelets to aort as from SP- treated rabbits was i ncreased (p < 0.025), PGI2 - like activity was partially inhibited, but over all adhesion of SP-treated platelets to aor tas f rom SP-treated animals reduced by 30% (p < 0.02). Adhesion to aortas of ASA- treated rabbits was sliahtly inc r ea=-.ed (p > 0 . 1) , PGI 2 - l ike act ivi ty abolished , and no overall reduc tion in platelet adhesion seen. DP had no effecton adhesion or PGI-like activity. These results support the evidence that cyclo-oxygenase inhibitors reduce the inherent resistance of the vessel wall to platelet adhesion. However with SP, inhibitory effects on platelets appear to be more important.

Phospholipase C from Clostridium Perfringens Induces Human Platelet Aggregation in Plasma

1988 ◽  
Vol 59 (02) ◽  
pp. 236-239 ◽  
Author(s):  
Giovanna Barzaghi ◽  
Chiara Cerletti ◽  
Giovanni de Gaetano
Keyword(s):  
Platelet Aggregation ◽  
Receptor Antagonist ◽  
Phospholipase C ◽  
Clostridium Perfringens ◽  
Human Platelet ◽  
Ex Vivo ◽  
Platelet Rich Plasma ◽  
Platelet Activating Factor ◽  
Inhibitory Effect ◽  
Thromboxane Receptor Antagonist

SummaryWe studied the aggregating effect of different concentrations of phospholipase C (PLC) (extracted from Clostridium perfringens) on human platelet-rich plasma (PRP). PRP was preincubated with PLC for 3 min at 37° C and the platelet aggregation was followed for 10 min. The threshold aggregating concentration (TAG) of PLC was 3-4 U/ml.We also studied the potentiation of PLC with other stimuli on platelet aggregation. Potentiating stimuli, such as arachidonic acid (AA), ADP. Platelet Activating Factor (PAF) and U-46619 (a stable analogue of cyclic endoperoxides) were all used at subthreshold concentrations. We also studied the possible inhibitory effect of aspirin, apyrase, TMQ, a prostaglandin endoper- oxide/thromboxane receptor antagonist and BN-52021, a PAF receptor antagonist. Only aspirin and apyrase were able to reduce aggregation induced by PLC alone and PLC + AA and PLC + ADP respectively. TMQ and BN-52021 were inactive. In ex vivo experiments oral aspirin (500 mg) partially inhibited platelet aggregation induced by PLC alone, PLC + AA and PLC + ADP 2 and 24 h after administration. Aspirin 20 mg for 7 days also reduced aggregation induced by PLC + AA.

Inhibitory Effect of Staphylokinase on Platelet Aggregation

1993 ◽  
Vol 70 (05) ◽  
pp. 834-837 ◽  
Author(s):  
Akira Suehiro ◽  
Yoshio Oura ◽  
Motoo Ueda ◽  
Eizo Kakishita
Keyword(s):  
Platelet Aggregation ◽  
Human Platelet ◽  
Degradation Products ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Effective Concentration ◽  
Inhibit Platelet Aggregation ◽  
Platelet Suspension ◽  
Washed Platelet ◽  
Human Platelet Aggregation

SummaryWe investigated the effect of staphylokinase (SAK), which has specific thrombolytic properties, on human platelet aggregation. Platelet aggregation induced with collagen was observed following preincubation of platelets in platelet-rich plasma (PRP) or washed platelet suspension (WP) with SAK at 37° C for 30 min. SAK inhibited platelet aggregation in PRP only at the highest examined concentration (1 x 10-4 g/ml). Although SAK did not inhibit platelet aggregation in WP which contained fibrinogen, it did when the platelets had been preincubated with SAK and plasminogen. The most effective concentration in WP was 1 x 10-6 g/ml. The effect could be inhibited by adding aprotinin or α2-antiplasmin. The highest generation of plasmin in the same preincubation fluid was detected at 1 x 10-6 g/ml SAK. We concluded that SAK can inhibit platelet aggregation in WP by generating plasmin and/or fibrinogen degradation products, but is only partially effective in PRP because of the existence of α2-antiplasmin.

The Effect of Barbituric Acid Derivatives on Platelet Function in Vitro and in Vivo

1973 ◽  
Vol 30 (02) ◽  
pp. 315-326
Author(s):  
J. Heinz Joist ◽  
Jean-Pierre Cazenave ◽  
J. Fraser Mustard
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Barbituric Acid ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Primary Response ◽  
Sodium Pentobarbital ◽  
Barbituric Acid Derivatives

SummarySodium pentobarbital (SPB) and three other barbituric acid derivatives were found to inhibit platelet function in vitro. SPB had no effect on the primary response to ADP of platelets in platelet-rich plasma (PRP) or washed platelets but inhibited secondary aggregation induced by ADP in human PRP. The drug inhibited both phases of aggregation induced by epinephrine. SPB suppressed aggregation and the release reaction induced by collagen or low concentrations of thrombin, and platelet adherence to collagen-coated glass tubes. The inhibition by SPB of platelet aggregation was readily reversible and isotopically labeled SPB did not become firmly bound to platelets. No inhibitory effect on platelet aggregation induced by ADP, collagen, or thrombin could be detected in PRP obtained from rabbits after induction of SPB-anesthesia.

The Effect of Collagen Mediated Platelet Release on Plasma Prekallikrein Activation

1984 ◽  
Vol 51 (01) ◽  
pp. 037-041 ◽  
Author(s):  
K M Weerasinghe ◽  
M F Scully ◽  
V V Kakkar
Keyword(s):  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Platelet Rich Plasma ◽  
Age Groups ◽  
Inhibitory Effect ◽  
Age Group ◽  
Platelet Factor ◽  
Activated Platelets ◽  
Platelet Release ◽  
Collagen Treatment

SummaryCollagen mediated platelet aggregation caused -5.6 ± 6.7% inhibition and +39.1 ± 15.2% potentiation of prekallikrein activation in plasma from normal healthy volunteers between 20–40 and 50–65 years of age, respectively (n = 15, p <0.01). The amouns of platelet factor-four (PF4) released in the two groups were not significantly different. Collagen treatment in the presence of indomethacin caused +11.5 ± 3.6% and +59.6 ± 19.5% potentiation in the 20–40 and 50–65 age groups respectively (p <0.02). Adrenaline mediated platelet aggregation caused -55.2 ± 7.1% and -35.2 ± 8.3% inhibition in the 20–40 and 50–65 age groups, respectively. Collagen treatment of platelet-deficient-plasma and platelet-rich-plasma in EDTA also caused potentiation of prekallikrein activation.The results indicate that the observed degree of prekallikrein activation after platelet aggregation is a net result of the inhibitory effect of PF4 and the potentiatory effect of activated platelets. The potentiatory effect was greater after collagen treatment as compared to adrenaline treatment, and in the 50–65 age group as compared to the 20–40 age group.

Effects of ovariectomy on aggregation, secretion, and metalloproteinases in porcine platelets

2003 ◽  
Vol 284 (5) ◽  
pp. H1679-H1685 ◽  
Author(s):  
Muthuvel Jayachandran ◽  
Whyte G. Owen ◽  
Virginia M. Miller
Keyword(s):  
Platelet Aggregation ◽  
Vessel Wall ◽  
Atp Release ◽  
Ovarian Hormones ◽  
Reticulated Platelets ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Atp Secretion ◽  
Sexually Mature ◽  
Wall Interactions ◽  
Expression And Activity

Differences in the aggregation and release of growth factors including matrix metalloproteinases (MMPs) after loss of ovarian hormones could contribute to an exaggerated response to injury in arteries of ovariectomized animals. Therefore, experiments were designed to compare aggregation, dense granular ATP release, expression of MMPs (MMP-2, MMP-9, and MMP-14) and tissue inhibitors of metalloproteinase (TIMP-1 and TIMP-2) in circulating platelets from sexually mature (7 mo old) gonadally intact and ovariectomized (4 wk) female pigs. Numbers of circulating platelets did not change after ovariectomy, but the percentage of reticulated platelets increased significantly. Platelet aggregation and dense granular ATP secretion also increased significantly with ovariectomy. In platelet lysates, active MMP-2 increased, whereas MMP-14 significantly decreased, after ovariectomy; the expression of TIMP-1, TIMP-2, and P-selectin did not change. These results suggest that platelet turnover, aggregation, and ATP secretion increase with ovariectomy. Also, ovarian hormones selectively regulate the expression and activity of MMPs in porcine platelets. Increased platelet aggregation and activity of MMP-2 would alter platelet-platelet and platelet-vessel wall interactions, contributing to an exaggerated response to injury with loss of ovarian hormones.

Platelet Retention in Glass Bead Columns: Further Evidence for the Importance of ADP

Blood ◽  
1974 ◽  
Vol 44 (3) ◽  
pp. 411-425 ◽  
Author(s):  
V. J. McPherson ◽  
M. B. Zucker ◽  
N. M. Friedberg ◽  
P. L. Rifkin
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Glass Bead ◽  
Room Temperature ◽  
Creatine Phosphokinase ◽  
Platelet Rich Plasma ◽  
Creatine Phosphate ◽  
Inhibitory Effect ◽  
Normal Platelet ◽  
Normal Individuals

Abstract Plasma of normal heparinized blood contained 0.284 µM ± SD 0.097 (ADP + ATP) with an ATP:ADP ratio of 2.5:1. Plasma from thrombocytopenic blood contained only 0.106 µM ± 0.073 (ADP + ATP). Blood with normal platelet retention released 0.234 µM ± 0.187 (ADP + ATP) during passage through a glass bead column, with an ATP:ADP ratio of 1.6:1. Significantly less was released in blood with low retention, i.e., samples from patients with von Willebrand’s disease, thrombasthenia, or thrombocytopenia, and some samples from normal individuals. Thus, nucleotides in the plasma of pre- and postcolumn blood appear to be derived from platelets; their release within glass bead columns is closely associated with normal platelet retention. Since release occurred at room temperature and was not prevented by acetylsalicylic acid or accompanied by measurable release of 14C-serotonin, the classic release reaction may not have been responsible. The low retention in platelet-rich plasma was variably increased by adding 0.5 µM ADP, an increase at least partly due to trapping of preformed aggregates. Retention in undisturbed blood was markedly inhibited by creatine phosphokinase with creatine phosphate (CPK-CP) and moderately inhibited by apyrase I (ATPase:ADPase 0.8:1) at an ADP-removing activity between 1 and 5 U/ml, indicating that ADP is essential for retention. At less than 1 U/ml, both apyrase I and II (ATPase: ADPase 2.8:1) enhanced retention in undisturbed blood, but CPK-CP was still inhibitory. These results suggest that enhancement is due to conversion of released ATP to ADP, as shown to occur in studies of platelet aggregation with ATP and ADP. At less than 1 U/ml, all three enzymes protected against the inhibitory effect of disturbance; this protection was marked with apyrase II, moderate with apyrase I and slight with CPK-CP. These observations provide additional evidence that ADP is responsible for the low retention caused by disturbance of the blood.

Inhibition of Human Platelet Aggregation by the Proteolytic Effect of Streptokinase (SK). Role of the Factor VIII Related Antigen

1975 ◽  
Author(s):  
R. Castillo ◽  
S. Maragall ◽  
J. A. Guisasola ◽  
F. Casals ◽  
C. Ruiz ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Factor Viii ◽  
Platelet Rich Plasma ◽  
Gel Filtration ◽  
Inhibitory Effect ◽  
Factor Viii Related Antigen ◽  
Human Factor Viii ◽  
Induced Aggregation

Defective ADP-induced platelet aggregation has been observed in patients treated with streptokinase. This same effect appears “in vitro” when adding SK to platelet rich plasma (PRP). Classic hemophilia and normal platelet poor plasmas (PPP) treated with SK inhibit the aggregation of washed platelets; plasmin-treated normal human serum also shows an inhibitory effect on platelet aggregation. However, von Willebrand SK-treated plasmas do not inhibit the aggregation of washed platelets. The same results appear when plasmas are previously treated with a rabbit antibody to human factor VIII.This confirms that the antiaggregating effect is mainly linked to the digested factor VIII related antigen.The inhibition of ADP-induced platelet aggregation has been proved in gel filtration-isolated and washed platelets from SK-treated PRP.Defective ristocetin-induced platelet aggregation has also been observed- This action does not appear in washed platelets from SK-treated PRP in presence of normal PPP, but it does in presence of SK-treated PPP, which suggests that the inhibition of the ristocetin-induced aggregation is due to the lack of factor VIII and not to the factor VIII-related products.Heparin, either “in vivo” or “in vitro”, has corrected the antiaggregating effect of SK.

Effect Of Factor XIII On Platelet Aggregation. Study Of Platelet Function And Fibrin Stabilization Inhibitors

1981 ◽  
Author(s):  
M Maamer ◽  
O Demay ◽  
M Aurousseau
Keyword(s):  
Platelet Aggregation ◽  
Acetylsalicylic Acid ◽  
Platelet Function ◽  
Factor Xiii ◽  
Platelet Rich Plasma ◽  
Inhibitory Effect ◽  
Photometric Method

There is little information on the participation of Factor XIII in platelet aggregation. Using BORN’s photometric method to study platelet aggregation induced by ADP in vitro on platelet rich plasma (PRP) of rabbit; clot solubility in 1 % monochloracetic acid and incorporation of dansylcadaverin into casein (LORAND L. et al.) to measure plasma FXIII concentration ; we showed that addition of activated F.XIII (F.XIIIa) to a PRP, aggregating power of platelets was significantly increased (+ 30.4 %, p<0.00l). Addition of inactive F.XIII or thrombin + Ca++ in concentrations used to activate F.XIII, had no significant effect on platelet aggregation induced by ADP.When F.XIIIa was added to plasma in presence of F.XIII inhibitors as 3178 AQ (a new synthetic benzothiophen keton derivative) or monodansylcadaverin (DC) in concentrations of (3.27 × 10-4 M and 9.31 × 10-4 m respectively), the platelet aggregation was significantly inhibited (- 48.8 % and - 35.4 % respectively, p<0.001). This inhibitory effect was not seen when dipyridamole or Acetylsalicylic Acid (ASA) in concentrations of (6.18 × 10-4 M and 17.3 × 10-4 M respectively) ware added in PRP in presence of F.XIIIa When platelet aggregation was performed without addition of F.XIIIa the inhibitory effect of 3178 AQ and DC was respectively (- 76.6 % and - 65.1 %, p<0.001), dipyridamole (- 37.6 %, p<0.00l) and ASA (-4.1%, no significant)These results suggest that F.XIIIa increased the platelet aggregation induced by ADP and compounds which are both inhibitors of platelet aggregation and F.XIII would be more potent antithrombotic by acting on platelets and fibrin stabilization, than drugs which are inhibitors of platelet aggregation only.

scholarly journals An Aorta Intima Inhibitor of Platelet Aggregation

1977 ◽  
Author(s):  
A.duP. Heyns ◽  
C.J. Badenhorst ◽  
F.P. Retief
Keyword(s):  
Platelet Aggregation ◽  
High Voltage ◽  
Vessel Wall ◽  
Prostaglandin Synthesis ◽  
Human Aorta ◽  
Intravascular Thrombosis ◽  
Wall Interaction ◽  
High Voltage Electrophoresis

The interaction of platelets and the vessel wall is of importance in the pathogenesis of intravascular thrombosis and atherosclerosis. We have previously described the presence of an inhibitor of platelet aggregation and a low Km ADPase in aorta intima extracts. The inhibitor was further characterized.Human aorta intimas were homogenized, centrifuged and supernatants used. Platelet aggregation was measured in a aggregometer.ADPase activity was measured by incubating 14C-ADP with intima, separating metabolites by high voltage electrophoresis and quantitated.Aggregation induced by ADP, collagen, Ristocetin and polylysine was inhibited by the intima extract. The inhibition was still evident in aspirin treated platelets. The inhibitor is present in the supernatant of 100 000g centrifuged extracts. This inhibitor appears not to be ADPase or the recently described prostacyclin (PGX) :- it is stable and not destroyed by incubation at 37°C, blocking of prostaglandin synthesis by pre-incubation of the intima with indomethacin has no effect on inhibitor activity.ADPase is inactivated by KCN whereas the inhibitor is not.The inhibitor of platelet aggregation and to a lesser extent ADPase, in the intima may be important regulators of platelet-vessel wall interaction.

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