With platelet activation, there is modulation of platelet surface molecule expression. In flow cytometric analyses of in vivo platelet activation, results are often confounded by activation induced in vitro by the preparative procedures. It is particularly important therefore to prevent or retard platelet activation as soon as possible after withdrawal of the blood sample. Taking blood into paraformaldehyde, or fixing the cells with paraformaldehyde as soon as possible after withdrawal, has been employed to prevent platelet activation in vitro, but paraformaldehyde-fixed platelets cannot be further used in functional studies. We investigated the efficacy of Diatube-H, a commercially available combination of platelet antagonists (theophylline, adenosine, and dipyridamole), in preventing or retarding platelet activation in vitro, along with its effects on modulation of platelet membrane glycoproteins (GP) and adhesion molecules. In contrast to blood taken into EDTA, blood taken into Diatube-H ...
Using a highly sensitive marker of platelet function, we have shown that platelet activation is increased in patients with stable COPD compared with controls matched for age and previous cigarette smoke exposure. Moreover, platelet activation is further increased in patients with COPD during an acute exacerbation. Taken together, these findings suggest that platelet function may be modified as a consequence of COPD.. We suggest that platelet activation represents a novel mechanism linking COPD, inflammation and cardiovascular disease. Platelet activation is known to predict an adverse outcome in patients with stable coronary disease15 and to identify patients likely to have recurrent cardiovascular events following percutaneous coronary intervention.16 The interaction between platelets and inflammatory cells stimulates release of chemokines and further recruitment of immune mediators which are central to the development of atherosclerotic plaque.. Platelet activation has also been implicated in ...
Our finding that mean platelet component is lower in acute myocardial infarction than in unstable angina, reflecting greater platelet activation, confirms the central role of thrombogenicity in the pathogenesis of acute coronary syndromes. Indeed, platelet activation was an independent predictor of the mode of presentation and, even in the subgroup of patients with unstable angina at high risk of future events, platelet activation was significantly lower than in those with myocardial infarction.. Some studies have not found a difference in platelet activation between unstable angina and myocardial infarction. However, Garlichs and colleagues2 found greater expression of the CD40 ligand in unstable angina than in myocardial infarction. This appears counterintuitive but may reflect greater hydrolysis and release of the ligand in myocardial infarction. Mathur and colleagues3 found a greater expression of P selectin in myocardial infarction than in unstable angina but also found that mean platelet ...
TY - JOUR. T1 - Inhibitory signaling of 17β-estradiol in platelet activation. T2 - The pivotal role of cyclic AMP-mediated nitric oxide synthase activation. AU - Wu, Gong-Jhe. AU - Lee, Jie Jen. AU - Chou, Duen-Suey. AU - Jayakumar, Thanasekaran. AU - Hsiao, George. AU - Chen, Wei Fan. AU - Sheu, Joen-Rong. PY - 2010/12/15. Y1 - 2010/12/15. N2 - Arterial thromboses are mostly composed of platelets adherent to ruptured endothelial surfaces. Platelets are anucleated cells; therefore, they represent an excellent and unique model to selectively investigate the signaling pathways mediating the nongenomic effects of estrogen. The aim of this study was to examine the signal transduction pathways of 17β-estradiol in preventing platelet activation. In this study, 17β-estradiol (5~10μM) exhibited more-potent activity of inhibiting platelet aggregation stimulated by collagen than other agonists (i.e., thrombin). 17β-Estradiol-inhibited collagen-stimulated platelet activation accompanied by [Ca2+]i ...
This thesis describes the Chandler loop, which makes it possible to conduct studies in vitro of molecular and cellular interactions between whole blood and stents. It was possible to monitor activation and inhibition of the cascades systems, leukocytes and platelets by combining different platelet inhibitors and heparin coating of stents. The clinical study was performed on patients with ACS undergoing PCI and stent implantation. In this study platelet activation markers P-selectin, and αIIb/β3 as well as inflammatory markers were followed from baseline during the first 48 hours post-PCI. The same parameters were evaluated in healthy controls for comparison at baseline. In vitro: The activation of blood in the Chandler loops were more pronounced for unmodified stent grafts than for partially heparin coated stent grafts. Heparin coated stent grafts dreated the same activation as the loops alone. This indicated that the Chandler loop system was a feasible tool for evaluation of blood compability ...
We investigated the effects of dietary polyunsaturated fatty acids (PUFAs) on blood lipids and processes that determine hemostatic potential: platelet activation, coagulation, and fibrinolysis. For 8 to 10 weeks, Wistar rats were fed a high-fat diet containing various amounts (2% to 16%) of n-3 PUFAs derived from fish oil (FO) or a diet enriched in n-6 PUFAs from sunflower seed oil (SO). Only the FO diets caused a reduction in mean platelet volume, platelet arachidonate level, and formation of thromboxane B2 by activated platelets, but neither of the diets had a measurable effect on platelet activation. The FO-rich diets decreased the plasma concentrations of triglycerides and cholesterol, whereas the SO diet reduced triglycerides only. Parameters of fibrinolysis and standard coagulation times, ie, activated partial thromboplastin time and prothrombin time, were only marginally influenced by these diets. In contrast, dietary FO, but not SO, led to decreased levels of the vitamin K-dependent ...
I have trouble collecting blood from mice for measuring platelet activation. The treatment with a drug is supposed to make platelets more active, but the non-treated controls show large deviation in platelet activation so no measurements are possible. Speaking with local experts helped a bit, but apparently they have the same problem. Apparently it is all about collecting the blood in a special way. Any ideas ...
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PAR1, PAR4 and GPIB form functional interdependent units in a receptor complex mediating platelet activation by thrombin in JOURNAL OF THROMBOSIS AND HAEMOSTASIS, vol 9, issue SI, pp 11-11 ...
Inappropriate platelet activation contributes to vascular diseases including stroke and myocardial ischemia. Our laboratory is focused on phospholipid signaling in platelets and its contribution to inappropriate platelet activation. Ongoing projects are directed at understanding the roles of pleckstrin and lipid kinases in platelets. Pleckstrin (p47) was once solely known as an early marker of platelet activation; more recently it has been noted to contain the prototypic Pleckstrin Homology motif. Over the past half dozen years, work derived from our laboratory has demonstrated that pleckstrin plays a dominant role in the reorganization of the platelet, and lymphocyte, cytoskeleton. Furthermore, our laboratory has established these effects are regulated by pleckstrin phosphorylation, require critical lipid-binding residues contained with the amino-terminal Pleckstrin Homology domain, and have implicated an effector for this process to be the small GTP-binding protein, Rac. Additional work from ...
It is now well-accepted that PAR1 and PAR4 have differential roles in platelet activation. PAR4, a low affinity thrombin receptor in human platelets, participates in sustained platelet activation in a P2Y12 dependent manner; however, the mechanisms are not defined. Our previous studies demonstrated that thrombin induces co-immunoprecipitation of PAR4 with P2Y12, together with arrestin recruitment to the complex. Here we show that PAR4 and P2Y12 directly interact to co-regulate arrestin-2 signaling following PAR4 activation. We observed direct and specific interaction of P2Y12 with PAR4, but not PAR1 by Bioluminescent Resonance Energy Transfer (BRET) when the receptors were co-expressed in HEK 293T cells. PAR4-P2Y12 dimerization was promoted by PAR4-AP and inhibited by P2Y12 antagonist. Using sequence comparison of the transmembrane domains of PAR1 and PAR4, we designed a mutant of PAR4: PAR4SFT, by replacing LGL194-196 at the base of transmembrane domain 4 with the corresponding aligned PAR1 ...
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There is a great need to improve our understanding of the molecular characteristics and heterogeneity of cancer. The NCI60 is a powerful tool for such studies, due to the wealth of data publicly available about those cell lines (1-6). Although much is known about the DNA, RNA, and pharmacologic aspects of the lines, data on protein expression and activation is much more limited. Previous proteomic analyses of the NCI60 have yielded important information, including the marked lack of correlation between protein and mRNA expression levels for several families of proteins (14, 18). However, those studies did not include a direct assessment of the activation status of signaling pathways. We have extended the available body of data available on the NCI60 by performing RPPA analysis using activation-specific markers for several cell-signaling pathways. We have used those data in concert with other available proteomic data to extend our understanding of the patterns of protein expression and activation ...
Overview for Balance Biosurface - provides reduced platelet activation and adhesion and preserves platelet function with a non-heparin coating.
The use of arachidonic acid (AA) to stimulate platelets is considered as a specific approach to study aspirin treatment efficacy. However, very high concentrations of AA are used, and it has been previously reported that AA can induce cell lysis in other settings. Several clinical studies have reported decreased responses to AA in whole blood tests in the presence of clopidogrel. Our aim was to investigate whether unspecific effects contribute to AA-induced aggregation and platelet activation in light transmission aggregometry (LTA) in platelet-rich plasma (PRP), and in assays using whole blood, multiple electrode aggregometry (MEA, Multiplate?), and flow cytometry. We report that cell lysis, especially of red blood cells, does occur at concentrations of AA used in the clinical tests and that ADP is very important for the AA-induced platelet activation responses. In flow cytometry, very limited platelet activation was detected before reaching AA concentrations in the millimolar range, where cell ...
This study is the first to show that platelet activation is increased by the brachytherapy currently applied in clinical practice. A notable increase was found after brachytherapy compared with PCI without irradiation. We have previously identified increased platelet activation after conventional PCI as an independent risk factor for acute ischaemic events.20 The data on radiation delivery devices submitted for US Food and Drug Administration (FDA) approval showed that patients treated with radiation benefit from a reduction in recurrent stenosis but also have the disadvantage of an increased rate of thrombotic events.192324 Thrombotic occlusions are associated with increased mortality after PCI21 and an increased risk of myocardial infarctions after VBT.1419232526 The increase in platelet activation after brachytherapy is not suppressed by concomitant treatment with aspirin and clopidogrel. Both drugs were given to all 23 patients three to four weeks before elective brachytherapy. In the group ...
Protease-activated receptors (PAR)-1 and -4 are the principal receptors for thrombin-mediated platelet activation. Functional genetic variation has been described in the human PAR1 gene, but not in the PAR4 gene (F2RL3). We sought to identify variants in and around F2RL3 and to determine their association with perioperative myocardial injury (PMI) after coronary artery bypass graft surgery. We further explored possible mechanisms for F2RL3 single nucleotide polymorphism (SNP) associations with PMI including altered receptor expression and platelet activation. Twenty-three SNPs in the F2RL3 gene region were genotyped in two phases in 934 Caucasian subjects. Platelets from 43 subjects (23 major allele, 20 risk allele) homozygous for rs773857 (SNP with the strongest association with PMI) underwent flow cytometry to assess PAR4 receptor number and response to activation by a specific PAR4 activating peptide (AYPGKF) measured by von Willebrand factor (vWf) binding and P-selectin release and PAC-1 ...
Postprandial hyperglycemia is associated with platelet activation. We thus investigated if meal-induced platelet activation could be attenuated by meal insulin. A randomized, double-blind, cross-over study was performed to compare postprandial platelet activation after premeal injections of placebo or insulin aspart (0.1 and 0.2 units/kg) in 18 patients with type 2 diabetes mellitus (T2DM). Platelet activation was assessed by flow cytometry, without and with stimulation by the thromboxane analog U46619 or ADP. Measurements were before and after premeal blood glucose standardization (to 6-7 mmol/L by insulin infusion, if needed) and at 90 min after the meal. Premeal insulin reduced postprandial hyperglycemia by 2-3 mmol/L compared with placebo. Postmeal insulin levels were doubled with placebo and further elevated with insulin injections. The standardized meal enhanced U46619-induced platelet P-selectin expression by 23% after placebo; this response was more than doubled after premeal insulin. ...
Second hand cigarette smoke (SHS) is one of the major risk factors for cardiovascular disease (CVD) and has been shown to substantiate platelet activation and aggregation in several studies [1, 2]. Most of these studies, under chronic or acute exposure conditions or over prolonged exposure, do not represent the initiation of a disease state or hematological damage under normal levels of cigarette smoke. These above studies of platelet activation with SHS together with our previous in-vitro studies demonstrating cardio-protective effects of nicotine [3], have motivated the present investigation of physiological levels of SHS exposure on human subjects and within an in-vitro endothelial cell-platelet system, with cigarettes (or smoke extracts) of varying nicotine content to confirm analogous cardio-protective effects of nicotine. ...
Second hand cigarette smoke (SHS) is one of the major risk factors for cardiovascular disease (CVD) and has been shown to substantiate platelet activation and aggregation in several studies [1, 2]. Most of these studies, under chronic or acute exposure conditions or over prolonged exposure, do not represent the initiation of a disease state or hematological damage under normal levels of cigarette smoke. These above studies of platelet activation with SHS together with our previous in-vitro studies demonstrating cardio-protective effects of nicotine [3], have motivated the present investigation of physiological levels of SHS exposure on human subjects and within an in-vitro endothelial cell-platelet system, with cigarettes (or smoke extracts) of varying nicotine content to confirm analogous cardio-protective effects of nicotine.. Copyright © 2007 by ASME ...
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current gold standard assay, namely platelet aggregation in stirring conditions in a platelet aggregometer. The microtiter plate (MTP) assay can detect ...
Platelets play a central role in maintaining biological hemostasis. Inappropriate platelet activation is responsible for thrombotic diseases such as myocardial infarction and stroke. Therefore, novel agents that can inhibit platelet activation are necessary. However, assays that monitor platelet aggregation are generally time-consuming and require high volumes of blood and specialized equipment. Therefore, a medium- to high-throughput assay that can monitor platelet aggregation would be considered useful. Such an assay should be sensitive, comparable to the "gold standard" assay of platelet aggregometry, and able to monitor multiple samples simultaneously but with low assay volumes. We have developed such a microtiter assay. It can assay an average of 60 independent treatments per 60 ml blood donation and demonstrates greater sensitivity than the current gold standard assay, namely platelet aggregation in stirring conditions in a platelet aggregometer. The microtiter plate (MTP) assay can detect ...
Tortuous blood vessels are often seen in humans in association with thrombosis, atherosclerosis, hypertension, and aging. Vessel tortuosity can cause high fluid shear stress, likely promoting thrombosis. However, the underlying physical mechanisms and microscale processes are poorly understood. Accordingly, the objectives of this study were to develop and use a new computational approach to determine the effects of venule tortuosity and fluid velocity on thrombus initiation. The transport, collision, shear-induced activation, and receptor-ligand adhesion of individual platelets in thrombus formation were simulated using discrete element method. The shear-induced activation model assumed that a platelet became activated if it experienced a shear stress above a relative critical shear stress or if it contacted an activated platelet. Venules of various levels of tortuosity were simulated for a mean flow velocity of 0.10 cm s−1 , and a tortuous arteriole was simulated for a mean velocity of 0.47 ...
Differences in expression of the platelet activation marker P-selectin (CD62P) between Fabry disease patients and healthy subjects at baseline and after agonist ...
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In pyroptosis experiments, nigericin can be used as a positive control to generate a robust caspase-1 activation response in a variety of cell lines.
In this study, we show that the platelet surface expression of glycoprotein (GP) V is regulated by two independent mechanisms. While confirming that both thrombin and neutrophil elastase proteolyse GPV, we show that neutrophil cathepsin G, thrombin receptor activating peptide (TRAP), and a combination of ADP and epinephrine can each result in a decrease in the platelet surface expression of GPV by a nonproteolytic mechanism: a cytoskeletal-mediated redistribution of platelet surface GPV to the surface-connected canalicular system (SCCS). Four independent lines of evidence documented the nonproteolytic nature of this decrease in the platelet surface expression of GPV. First, flow cytometric studies showed that cathepsin G, TRAP, and ADP/epinephrine decreased the platelet surface expression of GPV without changing the total platelet content of GPV. Second, immunoelectron microscopy directly demonstrated translocation of GPV from the platelet surface to the SCCS. Third, the cathepsin G-, TRAP-, and ADP
Introduction: S100A1 is a member of the S100 family of calcium-binding proteins. S100A1 controls Ca2+ dynamics in cardiomyocytes and plays an important role in heart failure. S100A1 is also strongly expressed in mouse platelets, but its role in platelet biology has not been investigated.. Goal: To determine the role of S100A1 in platelet activation and thrombosis.. Methods and Results: Platelet activation in response to threshold levels of convulxin, a specific agonist for the collagen receptor GPVI, showed significantly increased activation of αIIbβ3 integrin and α-granule release in S100A1-deficient (SKO) platelets compared with wild-type (WT) platelets. Consistently, SKO platelets also showed a more robust aggregation response to convulxin and collagen. In contrast, SKO platelets responded normally to stimulation with PAR4 receptor-activating peptide or ADP. Adhesion of SKO platelets to collagen under flow conditions was not significantly different to that of WT platelets. However, we ...
Results: 22 hypoxemic patients were selected for the study based on their diagnosis of COPD (from history and spirometry) along with age and sex matched controls. Presence of comorbidities and other factors that cause platelet activation were excluded. Level of platelet aggregation was determined by several experiments. By an aggregometer using platelet agonists (thrombin and ADP) it was found that platelet aggregation was significantly higher in hypoxemic COPD patients than normal healthy controls. Fluorescence spectrophotometer was used to measure intracellular calcium as a marker of platelet activation and it was found that hypoxemic COPD patients had significantly higher platelet aggregation than normal healthy controls. However no significant difference was found in other markers of platelet activation studied namely P-selectin exposure and PAC-1 binding between the two groups ...
In a previous report, we suggested that platelet hyperactivity, possibly through stimulated free radical-induced arachidonate acid metabolism, might be involved in the known thrombogenic risk of OC intake.15 We were also the first to show that dietary FD potentiated platelet activation.7 The present study was designed to determine whether FD could amplify OC effects and whether an impaired folate metabolism could contribute to the thrombogenicity of OC. We found that feeding rats with a folic acid-deficient diet enhanced OC-induced platelet hyperactivity. Although a rat model has been used with a high dose of estrogen that may not be comparable with that for women, we also observed that OC treatment led to a loss of folates associated with moderate hyperhomocysteinemia. We further suggested that involvement of an impaired folate metabolism in the prothrombotic effects caused by OC might be secondary to the OC-induced oxidative stress, which would initially affect platelet activity.. An effective ...
Patients with cancer have an increased risk of thromboembolism, which is the second leading cause of death in these patients. Several mechanisms of the prothrombotic state in these patients have been proposed. Among them are a platelet activation receptor, C-type lectin-like receptor 2 (CLEC-2), and its endogenous ligand podoplanin, which are the focus of this review. CLEC-2 is almost specifically expressed in platelets/megakaryocytes in humans. A membrane protein, podoplanin is expressed in certain types of cancer cells, including squamous cell carcinoma, brain tumor, and osteosarcoma, in addition to several normal tissues, including kidney podocytes and lymphatic endothelial cells but not vascular endothelial cells. In the bloodstream, podoplanin induces platelet activation by binding to CLEC-2 and facilitates hematogenous cancer metastasis and cancer-associated thrombosis. In an experimental lung metastasis model, the pharmacological depletion of CLEC-2 from platelets in mice resulted in a ...
inbook{d2d8fceb-9b60-4916-ad95-3b1f6f9113f7, abstract = {,p,Many pathogenic bacteria have been reported to interact with human platelets to mediate platelet activation and aggregation. The importance of these interactions to the immune response or pathogenesis of bacterial infection has not been clarified. It may therefore be valuable to assess platelet responses mediated by diverse strains of bacteria. Here, I describe a method to study platelet integrin activation and granule release using flow cytometry, and a complementary method to study platelet aggregation using a dedicated platelet aggregometer. The combination of these methods represents a rapid and cost-effective strategy to provide mechanistic insight on the type of platelet response mediated by the bacteria.,/p,}, author = {Shannon, Oonagh}, issn = {10643745}, keyword = {Bacteria,Coagulation,Flow cytometry,Platelets,Streptococci}, language = {eng}, pages = {267--273}, publisher = {Humana Press}, series = {Methods in Molecular ...
OBJECTIVES: We sought to examine whether patients with stable coronary artery disease (CAD) have increased platelet reactivity and an enhanced propensity to form monocyte-platelet aggregates. BACKGROUND: Platelet-dependent thrombosis and leukocyte infiltration into the vessel wall are characteristic cellular events seen in atherosclerosis. METHODS: Anticoagulated peripheral venous blood from 19 patients with stable CAD and 19 normal control subjects was incubated with or without various platelet agonists and analyzed by whole blood flow cytometry. RESULTS: Circulating degranulated platelets were increased in patients with CAD compared with control subjects (mean [+/- SEM] percent P-selectin-positive platelets: 2.1 +/- 0.2 vs. 1.5 +/- 0.2, p andlt; 0.01) and were more reactive to stimulation with 1 micromol/liter of adenosine diphosphate (ADP) (28.7 +/- 3.9 vs. 16.1 +/- 2.2, p andlt; 0.01), 1 micromol/liter of ADP/epinephrine (51.4 +/- 4.6 vs. 37.5 +/- 3.8, p andlt; 0.05) or 5 micromol/liter of thrombin
Full Text - The cardiovascular effects of testosterone and dihydrotestosterone are generally attributed to their modulatory action on lipid and glucose metabolism. However, no ex vivo studies suggest that circulating androgen levels influence the activation and reactivity of blood platelets - one of the main components of the haemostasis system directly involved in atherosclerosis. The levels of testosterone, dihydrotestosterone and oestradiol in plasma from men and women aged from 60 to 65 years were measured by LC-MS; the aim was to identify any potential relationships between sex steroid levels and the markers of platelet activation (surface membrane expression of GPII/IIIa complex and P-selectin) and platelet reactivity in response to arachidonate, collagen or ADP, monitored with whole blood aggregometry and flow cytometry. The results of the ex vivo part of the study indicate that the concentrations of testosterone and its reduced form, dihydrotestosterone are significantly negatively
The yellow fluid around tomato seeds appears to suppress platelet activation without affecting blood clotting. This anti-inflammatory effect may explain why eating tomato products is associated with lower cardiac mortality.
Altered platelet physiology may contribute to the emergence of thrombosis in patients with many forms of cardiovascular disease. Excess platelet activation may reflect increased stimulation of pro-aggregatory pathways. There is, however, increasing evidence that excessive platelet response, due to impaired efficacy of anti-aggregatory autacoids such as nitric oxide (NO) and prostacyclin (PGI2), may be just as important. For example, diminished platelet response to NO has been documented in acute and chronic myocardial ischaemia, heart failure, aortic valve disease and in the presence of hyperglycaemia. This "NO resistance" has been shown to reflect both the scavenging of NO by reactive oxygen species and dysfunction of its intracellular "receptor", soluble guanylate cyclase. Importantly, these abnormalities of NO signalling are potentially reversible through judicious application of pharmacotherapy. The analogous condition of impaired PGI2/adenylate cyclase (AC) signalling has received ...
Patent:. 1. Platelet activation markers as predictors of disease and of response to therapy and for monitoring therapeutic progress. (patent WO/2006/014958).Chapman S, Okrongly D, Ahnadi C.E, Wu A and Gervais A. Articles:. 1. Tsanaclis A, Grant A. Cognitive principles for visual integration of clinical information. Proc Adv. Health Inform Conf, 2012.. 2. Weiss, J.B., Grant, A., Marelli, A., Khairy, P., Maurais, T., Rehel, S., Chetaille, P., Broberg, C.S. Assessment of Electronic Health Information System Use and Need in US Adult Congenital Heart Disease Centers Congenital Heart Disease, 2011, 6(2): 134-138. 3. Paterson, G., Shaw, N., Grant, A., Leonard, K., Delisle, E., Mitchell, S., McCarrey, M., Pascal, B., Kraetschmer, N. A conceptual framework for analyzing how Canadian physicians are using electronic medical records in clinical care Studies in Health Technology and Informatics, 2010, 160(1):141-145. 4. Palm, J.-M., Grant, A., Moutquin, J.-M., Degoulet, P. Determinants of clinical ...
However, the molecular interactions are likely more complex, and certain conformations of nucleic acids appear to be more prone than others to forming multimolecular complexes with PF4. One example is the reactivity of the 44mer-DNA protein C aptamer vs the 77mer-RNA FMN aptamer. Although the latter is much longer and has more double-stranded segments (Figure 1A), anti-PF4/heparin antibodies bound somewhat more strongly to PF4/44mer-protein C aptamer complexes (Figure 5D).. Our data raise further questions beyond the scope of the current study. It remains unclear why only about 60% of the anti-PF4/heparin antibodies that induced platelet activation in the presence of heparin also caused platelet activation in the presence of nucleic acids. Even more puzzling is our observation that those sera that induced platelet activation in the presence of nucleic acids did so with most nucleic acids, independent of whether these strongly enhanced PF4 binding to the platelet surface or not. In the absence of ...
Rama Krishna Bontu Analysis of blood protein adsorption and platelet activation at biomaterial surfaces. University of Siegen Department of Analytical Chemistry and Institute of Functional Interfaces (IFG), Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany ...
ContextVariants in the CYP2C19 gene influence the pharmacologic and clinical response to the standard 75-mg daily maintenance dose of the antiplatelet drug clop
Primary and secondary prevention trials with statins, as well as with antiplatelet, clearly demonstrated that these drugs are able to reduce cardiovascular events. Even if the principal mechanism of action of statins is to lower cholesterol, other effects, the so-called pleiotropic effects, have been considered as adjunctive properties potentially accounting for the antiatherosclerotic effect of statins.. Inhibition of oxidative stress may be considered an intriguing pleiotropic effect in view of the fact that oxidative stress is thought to be a key event in the initiation and progression of atherosclerotic disease. Reduction of several markers of oxidative stress including isoprostanes, 8-hydroxydeoxyguanosine (8-OHdG), and nitrotyrosine have been observed after statin treatment. NADPH oxidase is among the most important sources of reactive oxygen species involved in atherosclerotic disease. The investigators developed an ELISA to evaluate serum levels of soluble-gp91phox, the catalytic core of ...
Cardiovascular disease and stroke are major causes of morbidity and mortality. Although many pathophysiological processes play a role in the development of vasc...
Although platelets can contribute to atherosclerosis and its thromboembolic complications in the nondiabetic population, the role of platelets in enhanced vascular disease in the diabetic population remains unclear. Most studies indicate that platelet function in vitro is enhanced in platelets from people and animals with diabetes, and the mechanisms are being identified. There remains some controversy about whether platelet changes occur before, and therefore could contribute to, vascular complications or whether they are secondary to vascular disease. It is possible that only intervention trials to determine if inhibiting platelet function limits the progression of vascular disease in diabetic patients will definitively answer this question. The earlier premise that enhanced activity of the arachidonate pathway is responsible for the hypersensitivity of platelets from diabetic humans needs to be modified to recognize that additional mechanisms are involved in platelet activation and are ...
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
CD36 is a membrane glycoprotein expressed on platelets, monocytes, macrophages, and several other cell types that was recently demonstrated to be involved in platelet activation in response to oxidized phospholipids, including oxidized LDL. Although the role of CD36 in other vascular cells has not been well defined, previous studies have demonstrated that cd36-knockout (cd36-/-) mice have prolonged thrombosis times after vascular injury, which can be protective in the state of hyperlipidemia. Here, we found significantly less ROS in the vessel walls of cd36-/- mice compared with WT after chemically induced arterial injury, suggesting that CD36 may contribute to ROS generation in the VSMCs themselves. Gene expression analysis revealed that the antioxidant enzymes peroxiredoxin-2 (Prdx2) and heme oxygenase-1 were upregulated in cd36-/- VSMCs. Molecular dissection of the pathway in isolated mouse VSMCs revealed CD36 ligand-dependent induction of Fyn phosphorylation, with subsequent phosphorylation ...
Local hemodynamics and its impact on the development of cardiovascular disease and the blood itself have gained increasing attention during the last decades. Regions with low and/or oscillatory Wall Shear Stress (WSS) have been correlated with increased risk for development of atherosclerosis [1]; and turbulence in the cardio vascular system is suggested to increase the risk for hemolysis as well as platelet activation and thrombus formation [2, 3]. Furthermore, turbulent flows are inherently oscillatory with large spatial as well as temporal fluctuation, and hence possibly a risk for atherosclerosis development per se.. ...
I have been involved with investigations in the field of thrombosis and hemostasis since joining the Brass lab at the University of Pennsylvania as a post-doctoral fellow in 2003. Since that time, the goal of my research studies has been to gain a better understanding of the mechanisms responsible for hemostasis and thrombosis, with a particular emphasis on how multiple signaling inputs present at a site of vascular injury are integrated to regulate platelet activation in vivo. The following is a brief summary of major ongoing projects performed in association with members of the Brass lab. In addition to these projects, I am involved in a number of collaborative studies with investigators at Penn, CHOP and other institutions across the country ...
... refers to the tendency of a material in contact with the blood to produce a thrombus, or clot. It not only refers to fixed
RNA test of blood platelets can detect, classify, and pinpoint the location of cancer by analyzing a sample equivalent to 1 drop of blood. Using this new method, researchers were able to identify cancer with 96% accuracy.
Oxidized LDL and platelets play a central role in the pathogenesis of atherosclerosis and ischemic cardiovascular diseases. Lysophosphatidic acid (LPA) is a thrombogenic substance that accumulates in mildly-oxidized LDL and in human atherosclerotic lesions, and is responsible for the initial platelet activation, shape change, induced by mildly-oxidized LDL and extracts of lipid-rich atherosclerotic plaques (Siess et al., 1999 Proc Natl Acad Sci USA 1999). LPA directly induced platelet shape change in blood and platelet-rich plasma (PRP) obtained from all blood donors. Albumin was one of the main inhibiting factors of platelet shape change in plasma. Interestingly LPA, at concentrations slightly above plasma levels, induced platelet shape change and aggregation in blood. 1-alkyl-LPA (16:0) was almost 20-fold more potent than 1-acyl-LPA (16:0). LPA-stimulated platelet aggregation in blood and PRP was donor-dependent. LPA-induced aggregation in blood could be completely blocked by the ADP- ...