Abstract:
:Human platelets synthesize nitric oxide (NO) through an endothelial-type NO synthase (ecNOS) activated also by substances enhancing 3',5'-cyclic adenosine monophosphate (cAMP) concentrations, such as catecholamines, beta-adrenoceptor agonists and adenosine. To verify whether cAMP directly activates ecNOS through the cAMP-dependent protein kinase A (PKA), we evaluated (i) the influence of 8-Br-cAMP, adenosine and forskolin on ecNOS activity and phosphorylation at Ser(1177) and (ii) the effect of PKA inhibition on ecNOS activity. Platelets from 10 healthy male volunteers were used for aggregation studies and measurement of NOS activity (conversion of L-[(3)H]-arginine to L-[(3)H]-citrulline) following exposure to 8-Br-cAMP, adenosine and forskolin, both in the absence and in the presence of the PKA inhibitor Rp-cAMPS (100 micromol/l). The phosphorylation of the PKA substrate vasodilator-stimulated phosphoprotein (VASP) at Ser(157) and Ser(239) and of ecNOS at Ser(1177) was evaluated by Western blot. NOS activity (pmol L-citrulline/10(8) platelets) increased from 0.090+/-0.002 to 0.148+/-0.013 with 500 micromol/l 8-Br-cAMP (p<0.0001), to 0.140+/-0.008 with 30 micromol/l adenosine (p<0.0001) and to 0.140+/-0.009 with 10 micromol/l forskolin (p<0.0001). Rp-cAMPS decreased baseline NOS activity from 0.093+/-0.001 to 0.075+/-0.006 (p<0.02) and prevented the stimulation by 8-Br-cAMP, adenosine and forskolin. Platelet exposure to 8-Br-cAMP and forskolin, beside the phosphorylation of the specific PKA substrate VASP, markedly increased the expression of ecNOS protein phosphorylated at Ser(1177). The study shows that NOS activity of human platelets is increased by the cAMP/PKA pathway which is involved in NO synthesis induced by adenosine, forskolin and potentially by every antiaggregating substance enhancing intraplatelet cAMP via receptor-dependent and -independent mechanisms.
journal_name
Thromb Resjournal_title
Thrombosis researchauthors
Russo I,Doronzo G,Mattiello L,De Salve A,Trovati M,Anfossi Gdoi
10.1016/j.thromres.2004.06.036subject
Has Abstractpub_date
2004-01-01 00:00:00pages
265-73issue
4eissn
0049-3848issn
1879-2472pii
S0049-3848(04)00347-0journal_volume
114pub_type
杂志文章abstract::This study comprised 50 patients subjected to major abdominal surgery, of which 13 developed deep vein thrombosis (DVT) according to the 125I-fibrinogen test. Plasma was sampled preoperatively, for the specific analysis of tissue plasminogen activator (t-PA) before and during venous occlusion. The recently described f...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(85)90103-3
更新日期:1985-07-15 00:00:00
abstract::Patients with essential hypertension (EH) and hyperhomocysteinemia (HHCY) suffer from more increased thrombotic events than those in EH alone. However, the underlying mechanisms for this effect are not well understood. This study hypothesized that neutrophil extracellular trap (NET) releasing may be triggered by HHCY ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2020.10.028
更新日期:2021-01-01 00:00:00
abstract::The effects of ticlopidine treatment (250 mg b.i.d. for 21 months) on fibrinogen and other rheological variables, as compared to placebo, were studied in 44 patients with intermittent claudication due to peripheral arterial occlusive disease. Blood samples were collected every 3 months during this double-blind, random...
journal_title:Thrombosis research
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/0049-3848(88)90134-x
更新日期:1988-12-15 00:00:00
abstract::A variant of type II von Willebrand disease (vWd) is described in a young woman and her mother with severe lifelong bleeding histories. On electrophoresis with low-resolution agarose gels the plasma of the proband lacked large and intermediate-size multimers of von Willebrand factor (vWF) but the platelet multimeric s...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90165-7
更新日期:1992-02-01 00:00:00
abstract::125I-fibronectin is incorporated into fibrin when blood plasma is clotted with thrombin. This process is dependent upon fibronectin concentration, temperature, and the presence of calcium ions. Fibronectin appears to be a very strong inhibitor of fibrin formation and influences both the thrombin clotting time and fibr...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(82)90308-5
更新日期:1982-09-01 00:00:00
abstract:BACKGROUND:Minimizing bleeding and transfusion is desirable given its cost, complexity and potential for adverse events. Concerns have been heightened by recent data demonstrating that bleeding events may predict worse outcomes and by warnings about the safety of erythropoietic stimulating agents. Prior small studies s...
journal_title:Thrombosis research
pub_type: 杂志文章,meta分析,评审
doi:10.1016/j.thromres.2008.09.015
更新日期:2009-03-01 00:00:00
abstract:INTRODUCTION:Nitric oxide (NO) plays an important role in the regulation of the cardiovascular system. It is produced by endothelial nitric oxide synthase (eNOS), which exhibits genetic polymorphisms. Although the clinically relevant polymorphism T(+IhI-786)C reduces eNOS-promoter activity, it is not clear whether circ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2004.09.003
更新日期:2005-01-01 00:00:00
abstract::Twenty-five men and 26 women were studied to investigate the effects of acute strenuous exercise on hemostasis after obtaining their informed consent. After familiarization, they performed exercise on a bicycle ergometer at 75% of their predetermined maximal workload until exhaustion. Bleeding time, measured by the Si...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(89)90058-3
更新日期:1989-08-15 00:00:00
abstract:INTRODUCTION:This study determines the impact of tissue factor (TF)-signaling on the extrinsic pathway of apoptosis in cancer cells and propose death associated protein kinase-1 (DAPK1) as a novel key regulator. MATERIALS AND METHODS:In MDA-MB-231 breast and PC3 prostate cancer cells, mRNA levels were analyzed by real...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2010.11.015
更新日期:2011-02-01 00:00:00
abstract::Biological effects of the modification of the sulphate ester and carboxyl group content of poly(vinyl alcohol-acrylic acid) copolymers (PAVAS) and sulphated polyvinyl alcohol copolymers (PVAS) with mol. weight of 5,000 to 20,000 D were studied. The in vitro anticoagulant potency of PAVAS assessed by activated partial ...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90154-6
更新日期:1994-05-15 00:00:00
abstract::The role of free radical generation and its scavenging enzymes in circulating mice polymorphonuclear leukocytes (PMNLs) has been studied following pulmonary thromboembolism. Levels of malonaldehyde (MDA), 02- radical generation, activity of superoxide dismutase (SOD), catalase (CAT), lactate dehydrogenase (LDH), myelo...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(92)90183-b
更新日期:1992-05-01 00:00:00
abstract::The enzymatic and fibrinolytic properties of glycosylated and nonglycosylated recombinant human pro-urokinase (pro-UK) produced in yeast Pichia pastoris were characterized and compared with those of Escherichia coli and mammalian cell-derived pro-UK. Among the five different forms of pro-UK, the yeast glycosylated pro...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/s0049-3848(00)00349-2
更新日期:2000-12-01 00:00:00
abstract:BACKGROUND:Arterial calcification is associated with increased risk of cardiovascular events. Osteoprotegerin (OPG) is a cytokine involved in the bone metabolism and vascular calcification. Recent data support a relationship between high serum levels of OPG and increased risk for cardiovascular disease in human. The ai...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2006.12.004
更新日期:2007-01-01 00:00:00
abstract:INTRODUCTION:Coagulation factor XIII (FXIII) is a fibrin-stabilizing factor, which contributes to hemostasis, wound healing, and maintenance of pregnancy. Accordingly, patients with congenital FXIII deficiency manifest a life-long bleeding tendency, abnormal wound healing and recurrent miscarriage. In order to understa...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.05.003
更新日期:2012-09-01 00:00:00
abstract::A Ca++-ionophore, ionomycin, increased the volume of human platelets suspended in a Ca++-containing buffer. This change in cell volume was dependent upon ionomycin and extracellular Ca++ concentrations, suggesting that the volume change occurs when the intracellular Ca++ reaches a certain level (greater than uM as det...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90197-k
更新日期:1990-01-01 00:00:00
abstract::Ondansetron is a 5-HT3 receptor antagonist with potent antiemetic, analgesic, and antiphlogistic effects. Literature concerning 5-HT3 antagonists on platelets is limited. In this report we examined the pharmacological effects of ondansetron on human washed platelets. Platelet aggregation induced by thrombin (0.1 U/mL)...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2012.06.003
更新日期:2012-09-01 00:00:00
abstract::Thrombin was acetylated by treatment with acetic anhydride, and the potency for protein C activation and the fibrinogen clotting activity of the resultant acetylthrombin were investigated in vitro and in vivo. The acetylthrombin retained an amidolytic activity to the synthetic substrate, S-2238, and reduced both of th...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(90)90053-f
更新日期:1990-08-15 00:00:00
abstract::Activation of human platelets by PAF was augmented by C-reactive protein, an acute phase plasma protein. The concentration of PAF required for irreversible activation (secondary aggregation of platelet and release of serotonin) was decreased to 1/10 in the presence of C-reactive protein (CRP). The presence of CRP stim...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(86)90361-0
更新日期:1986-03-01 00:00:00
abstract:INTRODUCTION:Platelets and the coagulation system may be involved in the pathogenesis of pre-eclampsia. We investigated whether platelet and coagulation activation markers, are elevated in pre-eclampsia. MATERIALS/METHODS:Case-control study in which activated platelets, platelet-monocyte/ neutrophil aggregates, platel...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2009.09.013
更新日期:2010-03-01 00:00:00
abstract::Effects of Ca2+ on phospholipid methylation in rabbit platelet membranes were studied using S-adenosyl-L-[3H-methyl]methionine as a substrate. The methylation was inhibited to 30% of the basal activity with 100 microM Ca2+. The inhibition was completely counteracted by various calmodulin antagonists. Their concentrati...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(83)90259-1
更新日期:1983-12-01 00:00:00
abstract:INTRODUCTION:Systemic embolism is the most serious complication of cardioversion of atrial fibrillation (AF) and the immediate post-cardioversion period is associated with increased risk for thrombus formation. For this reason, treatment with vitamin K antagonist (VKA) is recommended for patients with AF. No informatio...
journal_title:Thrombosis research
pub_type: 杂志文章,多中心研究
doi:10.1016/j.thromres.2011.08.031
更新日期:2012-05-01 00:00:00
abstract:INTRODUCTION:Quercetin is widely distributed in plants and has been reported to have effects of anti-inflammation and anti-thrombosis. In this study, we evaluated the protective effect of quercetin on LPS-induced experimental DIC in rabbits, and tried to clarify its mechanism against DIC. MATERIALS AND METHODS:LPS-ind...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.03.002
更新日期:2013-06-01 00:00:00
abstract::This study compared the responses of canine and human platelets to various aggregating agonists in the presence or absence of extracellular ATP and ATP analogues. Canine and human platelets were approximately equally reactive with ADP or collagen while the canine platelets were about 10 fold more sensitive to thrombin...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(93)90214-9
更新日期:1993-10-15 00:00:00
abstract::The cerebral vascular supply is constructed to protect the cerebral hemispheres and brainstem from the consequences of blood flow cessation. Reversal of blood flow around local obstructions is a feature of the microvascular beds of the striatum and cerebral cortex. Cerebral capillaries of these beds consist of endothe...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/s0049-3848(00)00218-8
更新日期:2000-05-01 00:00:00
abstract:OBJECTIVE:To compare rates of VTE occurrence in obese versus non-obese hospitalized patients who received UFH 5000 units subcutaneously q8 h. MATERIALS AND METHODS:This was a retrospective cohort study conducted in an academic medical center in the United States. Consecutive adult patients who were hospitalized during...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2018.07.027
更新日期:2018-09-01 00:00:00
abstract::Use of low molecular weight heparins (LMWHs) is now generally accepted as an ideal method of prophylaxis against postoperative venous thromboembolism. However, the long-term effects on the development of postthrombotic deep vein insufficiency are not known. Every patient developing such complications consumes a vast a...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/0049-3848(95)00232-4
更新日期:1996-01-01 00:00:00
abstract::Using a stable cross-linked SAK/plg complex, the effects of alpha 2-plasmin inhibitor on plasminogen activation by SAK were investigated. alpha 2-Plasmin inhibitor inhibited dose-dependently plasminogen activation by the SAK/plg complex. When FCB-2 or EACA was added to the reaction mixture of SAK/plg complex and alpha...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(94)90191-0
更新日期:1994-10-15 00:00:00
abstract::Cardiovascular disease (CVD) includes a number of conditions such as myocardial infarction, coronary heart disease, stroke, and venous thromboembolism. CVD is a leading health problem worldwide and a major cause of mortality, morbidity, and disability; it is also associated with high healthcare costs. The incidence of...
journal_title:Thrombosis research
pub_type: 杂志文章,评审
doi:10.1016/j.thromres.2014.11.036
更新日期:2015-02-01 00:00:00
abstract::The Fab fragment of a polyclonal antibody against platelet factor XIII inhibited the collagen-induced platelet aggregation in a dose-dependent manner. This inhibitory effect was specific for collagen, and it had no effect on arachidonic acid-, ADP-, and serotonin-induced aggregations. This finding strengthens our noti...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/0049-3848(88)90226-5
更新日期:1988-04-15 00:00:00
abstract:INTRODUCTION:Hydrogen sulfide (H2S) known as a gasotransmitter is increasingly recognized for its anti-adhesive, anti-inflammatory and vasoactive properties. Due to these properties, we analysed anti-thrombotic effects of H2S and the participation of the nitric oxide synthase (NOS)-pathway. MATERIALS AND METHODS:In in...
journal_title:Thrombosis research
pub_type: 杂志文章
doi:10.1016/j.thromres.2013.07.010
更新日期:2013-08-01 00:00:00