Modification Of Platelet Function Research Articles

Pleiotropic Beneficial Effects of Epigallocatechin Gallate, Quercetin and Delphinidin on Cardiovascular Diseases Associated with Endothelial Dysfunction

Cardiovascular diseases are an important public health problem because they represent a major cause of death worldwide. The pathophysiology of these chronic diseases is defined, among others, by an excess of reactive oxygen species production, a defect of endothelium-dependent vasodilation, a high blood pressure or a modification of platelet function. Epidemiological studies suggest that the beneficial cardiovascular health effects of diets rich in fruits and vegetables are, in part, mediated by their flavonoid content, with particular benefits provided by members of this family such as epigallocatechin gallate, quercetin or delphinidin. Many studies show that these phytochemicals are promising natural compounds to prevent cardiovascular diseases associated with endothelial dysfunction. Mechanistically, shortterm effects on endothelium-dependent vasodilation following the consumption of these flavonoids have been linked to an increased nitric oxide bioactivity. Moreover, besides their well-described antioxidant properties, these flavonoids are able to prevent endothelial cell apoptosis and to modulate various signaling pathways leading to inflammation. Therefore, this review attempts to outline our understanding about the pleiotropic beneficial effects of epigallocathecin gallate, quercetin or delphinidin on cardiovascular diseases associated with endothelial dysfunction. Furthermore, this review aims to identify the potential protective vascular effects of these flavonoids and their therapeutic value in cardiovascular medicine.

Platelet Aggregation and Adenosine Triphosphate Secretion in Dogs with Untreated Multicentric Lymphoma

Whole‐blood platelet aggregation and adenosine triphosphate secretion were measured in 15 dogs with untreated multicentric lymphoma and 10 normal control dogs to determine if dogs with lymphoma have altered platelet function. Dogs with quantitative platelet disorders (ie, thrombocytopenia or thrombocytosis) or with clinical evidence of a bleeding disorder were excluded from the study. Platelets from affected dogs had significantly greater maximum aggregation than those from control dogs, suggesting that platelets from dogs with lymphoma are hyperactive. Platelet hyperactivity may play a role in the development of hemostatic disorders (eg, disseminated intravascular coagulation) or in tumor metastasis. Further investigation is needed to determine if modification of platelet function in patients with lymphoma affects disease progression or outcome.

Platelet aggregation and adenosine triphosphate secretion in dogs with untreated multicentric lymphoma.

Whole-blood platelet aggregation and adenosine triphosphate secretion were measured in 15 dogs with untreated multicentric lymphoma and 10 normal control dogs to determine if dogs with lymphoma have altered platelet function. Dogs with quantitative platelet disorders (ie, thrombocytopenia or thrombocytosis) or with clinical evidence of a bleeding disorder were excluded from the study. Platelets from affected dogs had significantly greater maximum aggregation than those from control dogs, suggesting that platelets from dogs with lymphoma are hyperactive. Platelet hyperactivity may play a role in the development of hemostatic disorders (eg, disseminated intravascular coagulation) or in tumor metastasis. Further investigation is needed to determine if modification of platelet function in patients with lymphoma affects disease progression or outcome.

Modification of platelet function by isosorbide dinitrate in patients with coronary artery disease

The effect of a four weeks oral treatment with 100mg isosorbide dinitrate (ISDN) daily on platelet function was evaluated in 40 patients (aged 40–65 years) with proven coronary artery diseae. Isosorbide dinitrate decreased platelet reactivity to ADP (p < 0.001), increased platelet sensitivity to PGI2 (p < 0.01) while the production of TXB2 from exogenous arachidonic acid substrate and from endogenous substrate were both significantly reduced. Circulating platelet aggregates as measured by the Wu-test were markedly reduced (p < 0.001) but there was little change in the plasma concentration of the platelet proteins β-thromboglobulin and platelet factor 4. Overall, platelet activation correlated with smoking, hypertension and a family history of coronary artery disease. The reduced platelet activation seen during treatment with isosorbide dinitrate may contribute to the therapeutic benefit seen with this drug in patients with coronary artery disease.

Inhibition of lung colonization of mouse colon 26 adenocarcinoma by recombinant mouse interferon ? through a modification of platelet function

Recombinant murine interferon beta (MuIFN-beta) given i.v. efficiently inhibited both pulmonary arrest and formation of lung colonies of NL-17, a highly metastatic variant of mouse colon adenocarcinoma 26. NL-17 was rather resistant to MuIFN-beta in vitro and was highly resistant to natural killer cells of mice even though they were treated in vivo with MuIFN-beta. Platelets isolated from MuIFN-beta-treated mice showed reduced aggregating activity induced by NL-17. Since lung colonization by NL-17 is influenced by platelet aggregation, the inhibition of colonization by MuIFN-beta could be partly mediated through modification of platelet function in vivo. The effect of MuIFN-beta on platelet function and its subsequent inhibition of lung colony formation give new insights into the action of recombinant MuIFN-beta.

Modification of platelet function and arachidonic acid metabolism by bioflavonoids: Structure-activity relations

The mechanism of the antiaggregating activity of flavonoids was studied in vitro. The activity of fifteen different compounds was tested on platelet aggregation and arachidonic acid metabolism. The effect of flavonoids on platelet adenosine 3′,5′-cyclic monophosphate (cyclic AMP) levels under basal conditions, as well as after stimulation by prostacyclin (PGI 2), was also measured. The glycons of flavonoids in general and the flavanone derivatives that we tested did not affect platelet function. On the other hand, flavone, chrysin, apigenin and phloretin inhibited platelet aggregation by depressing the cyclooxygenase pathway. In addition, flavone, chrysin and apigenin reduced the platelet cyclic AMP response to PGI 2. This effect was probably mediated by an inhibition of adenylate cyclase. Myricetin and quercetin, however, increased the PGI 2-stimulated rise of platelet cyclic AMP. Both of these flavonoids inhibited primarily lipoxygenase activity. Modification of platelet cyclic AMP metabolism through inhibition of phosphodiesterase activity was found to be the probable mechanism of their antiaggregating effect.

Dipyridamole and aspirin in relation to platelet aggregation and vessel wall prostaglandin generation.

Modification of platelet function and vessel wall prostaglandin synthesis by pharmacologic intervention has attracted considerable attention. We report our observations on the effects of aspirin and dipyridamole alone and their combination on platelet aggregation and vessel wall prostacyclin (PGI2) generation. Although dipyridamole alone had no effects on platelet aggregation, it potentiated the platelet aggregation inhibitory effects of aspirin in vitro in a dose-related fashion. Dipyridamole also enhanced the platelet aggregation inhibitory effect of synthetic PGI2 in vitro. Potentiation of aspirin- and PGI2-induced platelet aggregation inhibition was observed in therapeutic range (5-10 micrograms/ml). In an isolated umbilical vein model dipyridamole stimulated release of PGI2 at much higher concentration (50-100 microgram/ml). Treatment of umbilical vein with aspirin (180 micrograms/ml) for 10 min blocked the spontaneous release of PGI2. In aspirin-treated umbilical vein segments dipyridamole treatment did not cause PGI2 release as in the untreated segments. These experiments suggest that although dipyridamole enhances both aspirin- and PGI2-induced platelet aggregation inhibition in clinically achieved concentrations, much higher levels are necessary for PGI2 release from intact human vessels. Furthermore, aspirin treatment of human vessels may prevent release of PGI2 in response to dipyridamole by blocking cyclooxygenase enzyme.

Modification of Platelet Function by Radical Species Produced During Irradiation of Oxygenated Water

Gel-filtered platelets in neutral, oxygen-containing solutions irradiated to a dose of 10 krad with gamma-rays display a significant inhibition of ADP-induced aggregation. Though the superoxide anion radical (O2-.) and H2O2 are generated in water irradiated under these conditions, only catalase, but not superoxide dismutase (SOD), conveyed protection against this inhibition of platelet function. When the platelets are in the presence of 10(-3) M sodium formate, which converts the majority of the radical species formed to O2-., inhibition of aggregation was again observed. Under these circumstances, the addition of catalase significantly decreased this inhibition, whereas the addition of SOD was without effect. In order to separate the platelet-inhibition effects of the radical species generated in the medium from a direct effect of irradiation on platelet components, relatively stable quantities of O2-. were produced in alkaline solutions and reacted with gel-filtered platelets. Again, an inhibition of ADP-induced aggregation was observed. This inhibition was not significantly altered by the addition of SOD, but was abolished by the addition of catalase, either with or without SOD. Our observation would indicate that O2-. is without direct effect on platelet function, but serves as the precursor of H2O2, which can inhibit platelet reactions.

Modification of platelet function by aspirin and dipyridamole across the myocardial vascular bed in coronary disease patients

Modification of platelet function by aspirin and dipyridamole across the myocardial vascular bed in coronary disease patients