Cigarette smoking and urinary excretion of markers for platelet/vessel wall interaction in healthy women

1991 ◽  
Vol 81 (1) ◽  
pp. 11-15 ◽  
Author(s):  
C. Rångemark ◽  
Å. Wennmalm
Keyword(s):  
Cigarette Smoking ◽  
Urinary Excretion ◽  
Platelet Activation ◽  
Vessel Wall ◽  
Thromboxane A2 ◽  
Epidemiological Studies ◽  
Thromboxane B2 ◽  
Platelet Activity ◽  
Healthy Women ◽  
Wall Interaction

1. Cigarette smoking is known to increase the risk of cardiovascular disease in both men and women. Experimental and epidemiological studies have demonstrated that cigarette smoking is associated with several indices of increased platelet activation and platelet/vessel wall interaction in men. The aim of the present study was to test the hypothesis that cigarette smoking is linked to an increased platelet activity in women also. 2. In 26 healthy smoking and non-smoking women (age 21–49 years) the urinary excretion of the thromboxane A2 metabolite 2,3-dinor-thromboxane B2 (an index of platelet activation) and of the prostacyclin metabolite 2,3-dinor-6-keto-prostaglandin F1α (an index of platelet/vessel wall interaction) were analysed by g.c.-m.s. in samples collected on days 3, 10 and 20 of their respective menstrual cycles. 3. The urinary excretion of 2,3-dinor-thromboxane B2 did not vary significantly during the menstrual cycle, either in the smokers or in the non-smokers. It was consistently higher (P < 0.004) in the group of smokers (average of days 3, 10 and 20, 395 ± 61 pg/mg of creatinine; mean ± sem) than in the group of non-smokers (average 188 ± 22 pg/mg of creatinine). 4. The urinary excretion of 2,3-dinor-6-keto-prostaglandin F1α did not differ between the groups on any of the days studied (average on days 3, 10 and 20 in the smokers and non-smokers was 281 ± 50 and 227 ± 30 pg/mg of creatinine, respectively). 5. These data demonstrate that smoking fertile women excrete more of the thromboxane A2 metabolite than do non-smokers, thereby supporting the hypothesis that cigarette smoking elicits platelet activation in healthy women. In contrast, platelet/vessel wall interaction does not appear to be facilitated in smoking compared with non-smoking women. The data suggest that platelet activation is not a major haemostatic mechanism during menstruation.

Cigarette Smoking Increases Thromboxane A2 Formation without Affecting Platelet Survival in Young Healthy Females

1992 ◽  
Vol 68 (05) ◽  
pp. 583-588 ◽  
Author(s):  
Annika Dotevall ◽  
Christina Rångemark ◽  
Elsa Eriksson ◽  
Jack Kutti ◽  
Hans Wadenvik ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Cigarette Smoking ◽  
Blood Cell ◽  
Urinary Excretion ◽  
Life Span ◽  
Cell Count ◽  
Thromboxane A2 ◽  
Blood Cell Count ◽  
Platelet Activity ◽  
Pai 1

SummarySmoking is a risk factor for the development of atherosclerotic cardiovascular disease, in men as well as in women. An increased urinary excretion of the thromboxane metabolite 2,3-dinor-thromboxane B2 (Tx-M) has been observed in smokers of both genders, suggesting that cigarette smoking may facilitate cardiovascular disease via an action on the platelets. The present study addressed the hypothesis that the increased Tx-M excretion in female smokers reflects a true facilitation of platelet reactivity in vivo, rather than an increased destruction of the platelets. In healthy female volunteers (aged 20–46 years, 18 smokers and 17 non-smokers) platelet life-span and indices of platelet activity were determined, together with plasma levels of plasminogen activator inhibitor-1 (PAI-1), fibrinogen, peripheral blood cell counts and hematocrit. The urinary excretion of Tx-M was higher in smokers than in non-smokers (361 vs. 204 pg/mg creatinine, respectively, p <0.05), while plasma and urinary β-thromboglobulin, plasma platelet factor 4, platelet mean life-span and platelet production rate did not differ between the groups. PAI-1 activity, white blood cell count and hematocrit were higher in smokers than in non-smokers (p <0.05). These data indicate that smoking facilitates platelet formation of thromboxane A2 without affecting platelet survival; i.e. it increases the activity of platelets without affecting their viability to a measurable extent. Such an increase in platelet activity, operating in parallel to a reduced fibrinolytic activity and a higher hematocrit and white blood cell count, may play an etiological role in smoking-induced cardiovascular disease in women.

scholarly journals Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis

2020 ◽  
Vol 21 (20) ◽  
pp. 7722
Author(s):  
Angela Dziedzic ◽  
Elzbieta Miller ◽  
Michal Bijak ◽  
Lukasz Przyslo ◽  
Joanna Saluk-Bijak
Keyword(s):  
Multiple Sclerosis ◽  
Mrna Expression ◽  
Platelet Activation ◽  
Blood Platelets ◽  
Surface Expression ◽  
Epidemiological Studies ◽  
Progressive Multiple Sclerosis ◽  
Apolipoprotein A1 ◽  
Platelet Activity ◽  
Activation Markers

Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for APOA1 and A2M genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet–platelet and platelet–leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for APOA1 and A2M genes.

PROSTACYCLIN AND THROMBOXANE A2 GENERATION IN VIVO IN MAN -EFFECT OF LOW DOSE ASPIRIN

1987 ◽  
Author(s):  
P A Kyrle ◽  
H G Eichler ◽  
K Lechner
Keyword(s):  
Vessel Wall ◽  
Low Dose ◽  
Bleeding Time ◽  
Thromboxane A2 ◽  
Significant Inhibition ◽  
Prostaglandin Metabolism ◽  
Dose Aspirin ◽  
Low Dose Aspirin ◽  
Wall Interaction

The effect of a low-dose aspirin regimen on platelet and vascular prostaglandin metabolism was studied in vivo in man. In a double-blind placebo-controlled cross-over study, 7 healthy male volunteers were treated with aspirin (35 mg.day−1 or placebo for 7 days. After a washout period of 2 weeks, the subject were crossed to the alternate treatment. 12 hours after the last dose of aspirin or placebo formation of thromboxane A2 (TxA2) and prostacyclin (FGI2) was measured in blood emerging from a standardized injury of the microvasculature made to determine bleeding time. TxA2 and PGI2 were measured as their stable degradation products, thromboxane B2 (TxB2) and 6-keto-prostaglandin F1α (6-keto PGF1α), using radioimmunoassay procedures. When subjects were treated with placebo, there was a rapid and substantial generation of both TxA2 and PGI2 at the site of plate-let-vessel wall interaction. This was reflected by an increase of TxB2 from 2.8±1 ng/ml and of 6-keto-PGF1α from 38.6±14.6pg/ml in the first minute to 4.5±0.6 ng/ml TxB2 and 154±50 pg/ml 6-keto-PGF1α after 4 minutes. Low-dose aspirin caused a significant inhibition of both TxA2 and PGI2 generation in bleeding time blood as represented by 65-92% and 81-84% inhibition of TxB2 and 6-keto-PGF1α Respectively throughout the 4 minute study period. We conclude that (a) rapid activation of both platelet prostaglandin metabolism and vascular PGI2 biosynthesis occurs at the site of platelet-vessel wall interaction and (b) low-dose aspirin results in a significant inhibition of platelet and vascular cyclo-oxygenase activity. Thus, our data fail to confirm the concept of a differential effect of low-dose aspirin on platelet and vascular prostaglandin synthesis in vivo in man.

Non-Invasive Assessment of the Cardiovascular Eicosanoids, Thromboxane A2 and Prostacyclin, in Randomly Sampled Males, with Special Reference to the Influence of Inheritance and Environmental Factors

1990 ◽  
Vol 79 (6) ◽  
pp. 639-645 ◽  
Author(s):  
Å. Wennmalm ◽  
G. Benthin ◽  
K. Caidahl ◽  
E. F. Granström ◽  
B. Lanne ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Vessel Wall ◽  
Acute Infection ◽  
Young Men ◽  
Thromboxane A2 ◽  
Platelet Activity ◽  
Recent Infection ◽  
Trained Subjects ◽  
Non Invasive ◽  
Noradrenaline And Adrenaline

1. We studied, in a random sample of 385 nonsmoking men born in 1968–1969 and 31 men born in 1913 or 1923, whether inheritance and environmental factors influenced platelet activity and vessel wall prostacyclin formation, as reflected non-invasively by the urinary excretion of the 2,3-dinor-metabolites of thromboxane A2 (2,3-dinor-thromboxane B2, Tx-M) and prostacyclin (2,3-dinor-6-keto-prostaglandin F1α, PGI-M), respectively. 2. Fathers of young men with high platelet activity did not excrete more Tx-M than fathers of young men with low platelet activity. Men born in 1913 or 1923 displayed higher Tx-M (563 versus 128 pg/mg of creatinine, P < 0.001) and PGI-M (163 versus 130 pg/mg of creatinine, P < 0.01) excretion than those born in 1968–1969. Excretion of both Tx-M and PGI-M was correlated to the urinary output of noradrenaline and adrenaline. 3. Well-trained subjects did not differ in their excretion of Tx-M or PGI-M from those who did not exercise regularly. A recent acute infection was also unrelated to the excretion of Tx-M or PGI-M. PGI-M excretion was, however, significantly correlated to Tx-M excretion (r = 0.51, P < 0.001). 4. This study provides the first non-invasive evidence that advancing age and sympathoadrenal tone are positively correlated to platelet activity in randomly sampled men, and that paternal inheritance, physical fitness and recent infection lack correlation to platelet activity.

Effect of Ridogrel on Vascular Contractions Gaused by Vasoactive Substances Released during Platelet Activation

1990 ◽  
Vol 64 (01) ◽  
pp. 091-096 ◽  
Author(s):  
W J Janssens ◽  
F J S Cools ◽  
L A M Hoskens ◽  
J M Van Nueten
Keyword(s):  
Smooth Muscle ◽  
Blood Vessel ◽  
Platelet Activation ◽  
Prostaglandin F2α ◽  
Thromboxane A2 ◽  
Femoral Arteries ◽  
Vasoactive Substances ◽  
Caudal Artery ◽  
Isolated Rat ◽  
Rat Platelets

SummaryRidogrel (6.3 × 10−6 to 10−4 M) inhibited contractions of isolated rat caudal arteries and rabbit femoral arteries caused by U-46619. The slope of an Arunlakshana-Schild plot (pA2-value: 3.4 × 10−6 M) on the caudal artery was slightly higher than one (1.14). This effect was maximal within}D min of incubation of the blood vessel with the compound and easily reversible. Ridogrel antagonised contractions of isolated rabbit femoral arteries caused by prostaglandin Fzo2α in the same concentration range. Ridogrel also inhibited contractions induced by aggregating rat platelets on isolated rat caudal arteries (itt the presence of ketanserin 4 × 10−7 M) and on isolated rabbit pulmonary and femoral arteries (in the absence of ketanserin). Ridogrel had no effect on Ca2+-induced contractions in depolarised isolated rabbit femoral arteries, and at 10−4 M antagonised serotonin-induced contractions in this blood vessel. Its effect on serotonin-induced contractions was statistically significant but very small on isolated rat caudal arteries. These observations indicate that ridogrel is an antagonist of prostaglandin endoperoxide/thromboxane A2 and prostaglandin F2α raCeptors on vascular smooth muscle.

Thrombin Inhibition and Thrombin Generation by Cultured Aortic Endothelial and Smooth Muscle Cells from Minipig

1982 ◽  
Vol 48 (01) ◽  
pp. 101-103 ◽  
Author(s):  
B Kirchhof ◽  
J Grünwald
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vessel Wall ◽  
Thrombin Generation ◽  
Muscle Cells ◽  
Thrombin Inhibition ◽  
Generating Capacity ◽  
Wall Interaction ◽  
Cells Cultured

SummaryEndothelial and smooth muscle cells cultured from minipig aorta were examined for their inhibitory activity on thrombin and for their thrombin generating capacity.Endothelial cells showed both a thrombin inhibition and an activation of prothrombin in the presence of Ca++, which was enhanced in the presence of phospholipids. Smooth muscle cells showed an activation of prothrombin but at a lower rate. Both coagulation and amidolytic micro-assays were suitable for studying the thrombin-vessel wall interaction.

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