1,720,985 research outputs found
Inibitori della cicloossigenasi e cardiopatia ischemica
No full texttrattazione rischio cardiovascoalre associato a uso di FAN
Platelet-Derived Extracellular Vesicles as Target of Antiplatelet Agents. What Is the Evidence?
Full text linkPlatelet-derived large extracellular vesicles (often referred to as microparticles in the field of cardiovascular disease) have been identified as effector in the atherothrombotic process, therefore representing a target of pharmacological intervention of potential interest. Despite that, limited evidence is so far available concerning the effects of antiplatelet agents on the release of platelet-derived extracellular vesicles. In the present narrative review, the mechanisms leading to vesiculation in platelets and the pathophysiological processes implicated will be discussed. This will be followed by a summary of the present evidence concerning the effects of antiplatelet agents under experimental conditions and in clinical settings
XXIV National Congress of the Italian Society for Thrombosis and Hemostasis - SISET: Abano Terme (PD), Italy 9-12 November 2016
No full textPlatelet microparticles are generated from activated platelets and have a role in arterial thromboembolism. Microparticles were isolated from healthy subjects and stimulate with arachidonic acid, ADP, a thrombin analogue, epinephrine or collagen in the presence or absence of ASA, the TP receptor antagonist SQ29548, apyrase and the P2Y12 inhibitor PBS-0739. Both ADP ans thromboxane A2 are required as amplifier of micropaticles shedding. The engagement of either the fibrinogen or the collagen receptor are necessarily implicated in microparticles generation
Exposure to Perfluoroalkyl Chemicals and Cardiovascular Disease: Experimental and Epidemiological Evidence
Full text linkPolyfluoro- and perfluoro–alkyl substances (PFAS) are organic chemicals extensively used worldwide for industry and consumer products. Due to their chemical stability, PFAS represent a major cause of environmental pollution. PFAS accumulate in animal and human blood and tissues exerting their toxicity. We performed a review of the epidemiological studies exploring the relationship between exposure to PFAS and thromboembolic cardiovascular disease. An increase in cardiovascular disease or death related to PFAS exposure has been reported from cross-sectional and longitudinal observational studies with evidence concerning the relation with early vascular lesions and atherosclerosis. Several studies indicate an alteration in lipid and glucose metabolism disorders and increased blood pressure as a possible link with cardiovascular thromboembolic events. We also examined the recent evidence indicating that legacy and new PFAS can be incorporated in platelet cell membranes giving a solid rationale to the observed increase risk of cardiovascular events in the populations exposed to PFAS by directly promoting thrombus formation. Exposure to PFAS has been related to altered plasma membrane fluidity and associated with altered calcium signal and increased platelet response to agonists, both in vitro and ex vivo in subjects exposed to PFAS. All the functional responses are increased in platelets by incorporation of PFAS: adhesion, aggregation, microvesicles release and experimental thrombus formation. These findings offer mechanistic support the hypothesis that platelet-centred mechanisms may be implicated in the increase in cardiovascular events observed in populations chronically exposed to PFAS
Antiplatelet Agents Inhibit The Generation Of Platelet-Derived Microparticles
Full text linkPlatelet microparticles (PMPs) contribute to thrombogenesis but the effects of antiplatelet drugs on PMPs generation is undefined. The present study investigated the cellular events regulating PMP shedding, testing in vitro platelet agonists and inhibitors. Platelet-rich plasma from healthy subjects was stimulated with arachidonic acid, U46619, collagen type-I (10 and 1.5 µg/mL), epinephrine, ADP or TRAP-6 and pre-incubated with acetylsalicylic acid (ASA, 100 and 10 µmol/L), SQ-29,548, apyrase, PSB-0739, or eptifibatide. PMPs were detected by flow-cytometry using CD61 and annexin-V as fluorescent markers. Platelet agonists induced annexin V-positive PMP shedding. The strongest response was to high concentration collagen. ADP-triggered PMP shedding was dose-independent. ASA reduced PMPs induced by arachidonic acid- (645, 347-2946 vs 3061, 446-4901 PMPs/µL; median ad range, n=9, P<0.001), collagen 10 µg/mL (5317, 2027-15935 vs 10252, 4187-46316 PMPs/µL; n=13, P<0.001), collagen 1.5 µg/mL (1078, 528-2820 vs 1465, 582-5948 PMPs/µL; n=21, P<0.001) and TRAP-6 (2008, 1621-2495 vs 2840, 2404-3031 PMPs/µL; n=3, P<0.01) but did not affect the response to epinephrine or ADP. The ADP scavenger apyrase reduced PMPs induced by U46619 (1256, 395-2908 vs 3045, 1119-5494 PMPs/µL, n=6, P<0.05), collagen 1.5 µg/mL (1006, 780-1309 vs 2422, 1839-3494 PMPs/µL, n=3, P<0.01) and TRAP-6 (904, 761-1224 vs 2840, 2404-3031 PMPs/µL, n=3, P<0.01). The TP receptor antagonist SQ-29,548 and the P2Y12 receptor antagonist PSB-0739 markedly inhibited PMPs induced by low doses of collagen. Except for high-dose collagen, eptifibatide abolished agonist-induced PMP release. Both TXA2 generation and ADP secretion are required as amplifiers of PMP shedding. The crucial role of the fibrinogen receptor and the collagen receptor in PMPs generation, independently of platelet aggregation, was identified
Elevated plasma levels of soluble TNF-alpha Receptor 1 (sTNFR1) in preeclampsia associated with fetal growth restriction
No full textIncreased concentration of TNFR is observed in plasma of preeclamptic women as compared to normtensive pregnant and non-oregnant women. This is related to indices of fetal growth restrictio
NCX-4016 (NO-aspirin) inhibits lipopolysaccharide-induced tissue factor expression in vivo: role of nitric oxide.
No full textBackground— NCX-4016 is an acetylsalicylic acid (ASA) derivative containing a nitric oxide–releasing moiety. Compared with ASA, NCX-4016 has a broader spectrum of antithrombotic and antiinflammatory activities. We hypothesized that NCX-4016 might inhibit in vivo lipopolysaccharide (LPS)-induced expression of tissue factor (TF).
Methods and Results— Rats were administered 90 mg/kg NCX-4016 orally for 5 days. Placebo, 50 mg/kg ASA, and 80 mg/kg isosorbide-5-mononitrate (ISMN) were used in control groups. On day 5, rats were injected intraperitoneally with 100 μg/kg LPS and killed 6 hours later. The expression of TF in monocytes was measured by flow cytometry and Western blot analysis. Reverse transcriptase–polymerase chain reaction was performed to assess expression of TF and cyclooxygenase-2 (COX-2) genes. Plasma concentrations of interleukin-1ß and tumor necrosis factor- were measured. Urine samples were collected to evaluate the excretion of the thromboxane metabolite 11-dehydro-thromboxane (TX)B2. Gastric mucosa was inspected. LPS injection was followed by synthesis TF and COX-2 mRNAs in circulating monocytes, which were blunted by NCX-4016 but not by ASA or ISMN. Both NCX-4016 and ISMN reduced TF expression on surface of circulating monocyte. LPS increased the excretion 11-dehydro-TXB2, and this was prevented by NCX-4016 and ASA. Unlike ASA, NCX-4016 reduced plasma interleukin-1ß and tumor necrosis factor-. In addition, NCX-4016 almost completely prevented mucosal damage, whereas ASA increased the extension of gastric lesions in LPS-injected rats.
Conclusions— NCX-4016 prevents monocyte TF expression; this is accompanied by inhibition of TX and cytokine biosynthesis. These additive effects of nitric oxide release and COX inhibition may help explain efficacy and tolerability of NCX-4016
Inhibition of TF expression on activated monocytes: potential role in the anti-thrombotic activity of NCX-4016
No full textNitroaspirin (NCX-4016) was shown able to inhibit tissue factor expression in human monocytes, in the animal model of LPS-induced inflammation and ex vivo in monocuytes from NCX-4016 treated healthy subjects. Inhibition of tissue factor expression and activity may be additive to the antiplatelet and antithrombotic effects of aspirin
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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