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.

ADP Signaling Defect in Children with Severe Acquired Aplastic Anemia: A Potential Common Pathway for Development of Aplastic Anemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3934-3934
Author(s):  
Jason C. Ford ◽  
Louis D. Wadsworth ◽  
Kirk R. Schultz
Keyword(s):  
Ulcerative Colitis ◽  
Platelet Aggregation ◽  
B Cells ◽  
Aplastic Anemia ◽  
Atp Release ◽  
Suppressive Therapy ◽  
Platelet Response ◽  
Knock Out ◽  
Atp Secretion ◽  
Immune Suppressive Therapy

Abstract Severe Acquired Aplastic Anemia is a rare disease with an incidence in British Columbia of 6.9 per million/year in Eastern/Southeastern Asians, 7.3 per million/year in South Asians and 1.7 per million/year in those of White/mixed ethnic descent. Two children presented with mucosal bleeding >4 years after achieving complete remission with immune suppressive therapy (antithymocyte globulin, cyclosporin A and prednisone). Evaluation revealed normal routine coagulation profiles and normal platelet numbers but mildly prolonged bleeding times (patients 8.5 - 11.0 minutes; control 3.0 – 8.0 minutes) and abnormal platelet aggregation as measured by aggregometry (optical and luminescence) after ADP stimulation. The patients had normal aggregation and ATP secretion after stimulation with thrombin (ATP secretion only), collagen, epinephrine, arachidonic acid, and ristocetin (1.125, 1.0, and 0.5 mg/mL concentrations, optical aggregation only) but showed abnormal aggregation with ADP (2.5, 5.0, and 10 μM). An additional 4 aplastic anemia patients were tested >1 year after successful immune suppressive therapy with no bleeding history: 1 of the 4 had the identical defect in platelet aggregation and ATP release after ADP stimulation, with no other defects on aggregometry. All 3 patients with abnormal platelet aggregation were of South or East Asian background, and the 3 with normal aggregation were of Caucasian/mixed ethnicity. Of the patients with an abnormal ADP platelet response, one has subsequently developed ulcerative colitis. Based on these observations we hypothesize that some patients with severe acquired aplastic anemia have an underlying defect in a signaling pathway shared by platelets, T cells, and B cells. ADP-induced signaling in platelets is induced through the surface molecule P2Y12, which is not expressed on lymphocytes. P2Y12 signaling occurs in association with a G protein Galphai2, an important signaling molecule in T and B cells and associated with development of ulcerative colitis in Galphai2 knock out mice. The specific signaling defect in platelets is currently being elucidated in these patients, and the incidence of these defects in aplastic anemia patients must be characterized.

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.

Sex-specific changes in platelet aggregation and secretion with sexual maturity in pigs

2004 ◽  
Vol 97 (4) ◽  
pp. 1445-1452 ◽  
Author(s):  
Muthuvel Jayachandran ◽  
Hiroya Okano ◽  
Ritu Chatrath ◽  
Whyte G. Owen ◽  
Joseph P. McConnell ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Sexual Maturity ◽  
Gonadal Hormones ◽  
Mature Adult ◽  
Reactive Protein ◽  
Fibrinogen Receptor ◽  
Atp Secretion ◽  
Children And Young Adults ◽  
Turbidimetric Analysis ◽  
Sexually Mature

Cardiovascular disease may begin early in adolescence. Platelets release factors contributing to vascular disease. Experiments were designed to test the hypothesis that hormonal transitions associated with sexual maturity differentially affect platelet aggregation and secretion in males and females. Platelets were collected from juvenile (2–3 mo) and sexually mature (adult; 5–6 mo) male and female pigs ( n = 8/group). Maturation was evidenced by increased weight of reproductive tissue and changes in circulating levels of gonadal hormones. Aggregation to ADP (10 μM) and collagen (6 μg/ml) and ATP secretion to 50 nM thrombin were determined by turbidimetric analysis and bioluminescence, respectively. Total platelet counts, platelet turnover, and mean platelet volume did not change with maturity. Platelet aggregation and ATP secretion decreased in females but increased in males with maturity, whereas total ATP content remained unchanged in platelets from females but increased in platelets from males. Platelet fibrinogen receptor, P-selectin expression, and receptors for sex steroids did not change with sexual maturation. Plasma C-reactive protein and brain-type natriuretic peptide also did not change. Results indicate that changes in platelet aggregation and secretion change with sexual maturity differently in females and males. These observations provide evidence on which clinical studies could be designed to examine platelet characteristics in human children and young adults.

Chlorobutanol, a Preservative of Desmopressin, Inhibits Human Platelet Aggregation and Release In Vitro

1990 ◽  
Vol 64 (03) ◽  
pp. 473-477 ◽  
Author(s):  
Shih-Luen Chen ◽  
Wu-Chang Yang ◽  
Tung-Po Huang ◽  
Shiang Wann ◽  
Che-ming Teng
Keyword(s):  
Arachidonic Acid ◽  
Platelet Aggregation ◽  
Atp Release ◽  
Free Calcium ◽  
Dependent Manner ◽  
Antiplatelet Effect ◽  
Human Platelet Aggregation ◽  
Acid Pathway ◽  
Arachidonic Acid Pathway

SummaryTherapeutic preparations of desmopressin for parenteral use contain the preservative chlorobutanol (5 mg/ml). We show here that chlorobutanol is a potent inhibitor of platelet aggregation and release. It exhibited a significant inhibitory activity toward several aggregation inducers in a concentration- and time-dependent manner. Thromboxane B2 formation, ATP release, and elevation of cytosolic free calcium caused by collagen, ADP, epinephrine, arachidonic acid and thrombin respectively were markedly inhibited by chlorobutanol. Chlorobutanol had no effect on elastase- treated platelets and its antiplatelet effect could be reversed. It is concluded that the antiplatelet effect of chlorobutanol is mainly due to its inhibition on the arachidonic acid pathway but it is unlikely to have a nonspecitic toxic effect. This antiplatelet effect of chlorobutanol suggests that desmopressin, when administered for improving hemostasis, should not contain chlorobutanol as a preservative.

Trimucytin: A Collagen-Like Aggregating Inducer Isolated from Trimeresurus mucrosquamatus Snake Venom

1993 ◽  
Vol 69 (03) ◽  
pp. 286-292 ◽  
Author(s):  
Che-Ming Teng ◽  
Feng-Nien Ko ◽  
Inn-Ho Tsai ◽  
Man-Ling Hung ◽  
Tur-Fu Huang
Keyword(s):  
Platelet Aggregation ◽  
Snake Venom ◽  
Inositol Phosphate ◽  
Shape Change ◽  
Platelet Activating Factor ◽  
Atp Release ◽  
Platelet Membrane ◽  
Thromboxane B2 ◽  
Dependent Manner ◽  
Concentration Dependent Manner

SummaryTrimucytin is a potent platelet aggregation inducer isolated from Trimeresurus mucrosquamatus snake venom. Similar to collagen, trimucytin has a run of (Gly-Pro-X) repeats at the N-terminal amino acids sequence. It induced platelet aggregation, ATP release and thromboxane formation in rabbit platelets in a concentration-dependent manner. The aggregation was not due to released ADP since it was not suppressed by creatine phosphate/creatine phosphokinase. It was not either due to thromboxane A2 formation because indomethacin and BW755C did not have any effect on the aggregation even thromboxane B2 formation was completely abolished by indomethacin. Platelet-activating factor (PAF) was not involved in the aggregation since a PAF antagonist, kadsurenone, did not affect. However, RGD-containing peptide triflavin inhibited the aggregation, but not the release of ATP, of platelets induced by trimucytin. Indomethacin, mepacrine, prostaglandin E1 and tetracaine inhibited the thromboxane B2 formation of platelets caused by collagen and trimucytin. Forskolin and sodium nitroprusside inhibited both platelet aggregation and ATP release, but not the shape change induced by trimucytin. In quin-2 loaded platelets, the rise of intracellular calcium concentration caused by trimucytin was decreased by 12-O-tetradecanoyl phorbol-13 acetate, imipramine, TMB-8 and indomethacin. In the absence of extracellular calcium, both collagen and trimucytin caused no thromboxane B2 formation, but still induced ATP release which was completely blocked by R 59022. Inositol phosphate formation in platelets was markedly enhanced by trimucytin and collagen. MAB1988, an antibody against platelet membrane glycoprotein Ia, inhibited trimucytinand collagen-induced platelet aggregation and ATP release. However, trimucytin did not replace the binding of 125I-labeled MAB1988 to platelets. Platelets pre-exposed to trimucytin were resistant to the second challenge with trimucytin itself or collagen. It is concluded that trimucytin may activate collagen receptors on platelet membrane, and cause aggregation and release mainly through phospholipase C-phosphoinositide pathway.

Interactions of Staphylokinase with Human Platelets

1995 ◽  
Vol 73 (03) ◽  
pp. 472-477 ◽  
Author(s):  
H R Lijnen ◽  
B Van Hoef ◽  
D Collen
Keyword(s):  
Platelet Aggregation ◽  
Platelet Function ◽  
Specific Binding ◽  
Platelet Rich Plasma ◽  
Human Platelets ◽  
Normal Plasma ◽  
Atp Secretion ◽  
Platelet Disaggregation ◽  
Activation Rate

SummaryThe interactions of recombinant staphylokinase (SakSTAR) with human platelets were investigated in a buffer milieu, in a human plasma milieu in vitro, and in plasma from patients with acute myocardial infarction (AMI) treated with SakSTAR.In a buffer milieu, the activation rate of plasminogen by SakSTAR or streptokinase (SK) was not significantly altered by addition of platelets. Specific binding of SakSTAR or SK to either resting or thrombin- activated platelets was very low. ADP-induced or collagen-induced platelet aggregation in platelet-rich plasma (PRP) was 94 ± 2.7% or 101 ± 1.7% of control in the presence of 0.1 to 20 μM SakSTAR, with corresponding values of 95 ± 2.8% or 90 ± 4.6% of control in the presence of 0.1 to 4 μM SK. No effects were observed on platelet disaggregation. ATP secretion following collagen-induced platelet aggregation was 4.3 ± 0.26 μM for SakSTAR (at concentrations of 0.1 to 20 μM) and 4.4 ± 0.35 μM for SK (at concentrations of 0.1 to 4 μM), as compared to 3.4 ± 0.70 μM in the absence of plasminogen activator.Fifty % lysis in 2 h (C50) of 60 μl 125I-fibrin labeled platelet-poor plasma (PPP) clots prepared from normal plasma or from plasma of patients with Glanzmann thrombasthenia and immersed in 0.5 ml normal plasma, was obtained with 12 or 16 nM SakSTAR and with 49 or 40 nM SK, respectively. C50 values for lysis of 60 μl PRP clots prepared from normal or patient plasma were also comparable for SakSTAR (19 or 21 nM), whereas SK was 2-fold more potent toward PRP clots prepared from Glanzmann plasma as compared to normal plasma (C50 of 130 versus 270 nM).No significant effect of SakSTAR on platelet function was observed in plasma from patients with AMI treated with SakSTAR, as revealed by unaltered platelet count, platelet aggregation and ATP secretion.Thus, no effects of high SakSTAR concentrations were observed on human platelets in vitro, nor of therapeutic SakSTAR concentrations on platelet function in plasma.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

Platelet-vessel wall interactions: Implication of 5-hydroxytryptamine. A review

1984 ◽  
Vol 15 (5-6) ◽  
pp. 612-626 ◽  
Author(s):  
F. Clerck ◽  
J. M. Nueten ◽  
R. S. Reneman
Keyword(s):  
Vessel Wall ◽  
Wall Interactions

Endothelial glycocalyx thickness and platelet-vessel wall interactions during atherogenesis

2011 ◽  
Vol 106 (11) ◽  
pp. 939-946 ◽  
Author(s):  
Mirjam oude Egbrink ◽  
Viviane Heijnen ◽  
Remco Megens ◽  
Wim Engels ◽  
Hans Vink ◽  
...  
Keyword(s):  
Vessel Wall ◽  
Laser Scanning ◽  
Ex Vivo ◽  
Laser Scanning Microscopy ◽  
Endothelial Glycocalyx ◽  
Knock Out ◽  
Two Photon ◽  
Common Carotid Arteries ◽  
Wall Interactions

SummaryThe endothelial glycocalyx (EG), the luminal cover of endothelial cells, is considered to be atheroprotective. During atherogenesis, platelets adhere to the vessel wall, possibly triggered by simultaneous EG modulation. It was the objective of this study to investigate both EG thickness and platelet-vessel wall interactions during atherogenesis in the same experimental model. Intravital fluorescence microscopy was used to study platelet-vessel wall interactions in vivo in common carotid arteries and bifurcations of C57bl6/J (B6) and apolipoprotein E knock-out (ApoE-/-) mice (age 7 – 31 weeks). At the same locations, EG thickness was determined ex vivo using two-photon laser scanning microscopy. In ApoE-/- bifurcations the overall median level of adhesion was 48 platelets/mm2 (interquartile range: 16 – 80), which was significantly higher than in B6 bifurcations (0 (0 – 16), p = 0.001). This difference appeared to result from a significant age-dependent increase in ApoE-/- mice, while no such change was observed in B6 mice. At the same time, the EG in ApoE-/- bifurcations was significantly thinner than in B6 bifurcations (2.2 vs. 2.5 μm, respectively; p < 0.05). This resulted from the fact that in B6 bifurcations EG thickness increased with age (from 2.4 μm in young mice to 3.0 μm in aged ones), while in bifurcations of ApoE-/- mice this growth appeared to be absent (2.2 μm at all ages). During atherogenesis, platelet adhesion to the wall of the carotid artery bifurcation increases significantly. At the same location, EG growth with age is hampered. Therefore, glycocalyx-reinforcing strategies could possibly ameliorate atherosclerosis.

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