Enhancement of platelet function by superoxide anion.

Handin, Robert I.; Karabin, Richard; Boxer, Grace Jordison

doi:10.1172/jci108718

Cited by 177 publications

(73 citation statements)

References 27 publications

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“…Our studies, together with those of others (8,22,33), suggest that activated PMN might influence platelets by several mechanisms, including superoxide anion, H202,or the MPO-H202-halide system. Further, the effect on platelets may be primary, i.e., initiation of release reactions, or secondary, i.e., impairment of the response to other stimuli.…”

Section: Methodssupporting

confidence: 77%

“…Under these conditions, H202 caused inhibition of shape change, primary aggregation, and secretion of constituents of dense granules and a-granules only if the decrease in adenylate energy charge exceeded 5%. Handin et al (33) described the initiation of platelet aggregation and serotonin release by xanthine oxidase, a superoxidegenerating enzyme. Inhibition of these effects by superoxide dismutase, but not catalase or mannitol, suggested mediation by superoxide rather than H202 or hydroxyl radical.…”

Section: Methodsmentioning

confidence: 99%

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Myeloperoxidase-Mediated Platelet Release Reaction

Clark¹,

Klebanoff²

1979

J. Clin. Invest.

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A B S T R A C T The ability of the neutrophil myeloperoxidase-hydrogen peroxide-halide system to induce the release of human platelet constituents was examined. Both resulted in a small, although significant, release ofboth serotonin and adenine, suggesting some platelet lysis. Substantial release of these markers was observed only with increased H202 concentrations (>0.1 mM) or prolonged incubation (1-2 h).Serotonin release by H202 was markedly enhanced by the addition ofmyeloperoxidase and a halide. Under these conditions, there was a predominance of release of serotonin (50%) vs. adenine (13%), suggesting, in part, a nonlytic mechanism. Serotonin release by the complete peroxidase system was rapid, reaching maximal levels in 2-5 min, and was active at H202 concentrations as low as 10 ,uM. It was blocked by agents which inhibit peroxidase (azide, cyanide), degrade H202 (catalase), chelate Mg2+ (EDTA, but not EGTA), or inhibit platelet metabolic activity (dinitrophenol, deoxyglucose).These results suggest that the myeloperoxidase system initiates the release of platelet constituents primarily by a nonlytic process analogous to the platelet release reaction. Because components of the peroxidase system (myeloperoxidase, H202) are secreted by activated neutrophils, the reactions described here may have implications for neutrophilplatelet interaction in sites of thrombus formation.Portions of this work have appeared in abstract form: Clin.

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Section: Methodssupporting

confidence: 77%

Section: Methodsmentioning

confidence: 99%

Myeloperoxidase-Mediated Platelet Release Reaction

Clark¹,

Klebanoff²

1979

J. Clin. Invest.

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“…These radicals increase the vascular tone, either through direct modulation of vasoconstrictive pathways or inactivation of NO, providing another possible mechanism of Hb-induced vasoactivity (43)(44)(45). Hb-derived free radicals can potentially activate platelets, and markers of platelet activation were indeed found to be increased in patients with sickle-cell disease (46,47). Platelet-released mediators like serotonin could therefore be another NO-independent cause of vascular complications in hemolytic anemias (48,49).…”

Section: Discussionmentioning

confidence: 99%

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Boretti¹,

Buehler²,

D’Agnillo³

et al. 2009

J. Clin. Invest.

133

178

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Release of hemoglobin (Hb) into the circulation is a central pathophysiologic event that contributes to morbidity and mortality in chronic hemolytic anemias and severe malaria. These toxicities arise from Hb-mediated vasoactivity, possibly due to NO scavenging and localized tissue oxidative processes. Currently, there is no established treatment that targets circulating extracellular Hb. Here, we assessed the role of haptoglobin (Hp), the primary scavenger of Hb in the circulation, in limiting the toxicity of cell-free Hb infusion. Using a canine model, we found that glucocorticoid stimulation of endogenous Hp synthesis prevented Hb-induced hemodynamic responses. Furthermore, guinea pigs administered exogenous Hp displayed decreased Hbinduced hypertension and oxidative toxicity to extravascular environments, such as the proximal tubules of the kidney. The ability of Hp to both attenuate hypertensive responses during Hb exposure and prevent peroxidative toxicity in extravascular compartments was dependent on Hb-Hp complex formation, which likely acts through sequestration of Hb rather than modulation of its NO-and O 2 -binding characteristics. Our data therefore suggest that therapies involving supplementation of endogenous Hb scavengers may be able to treat complications of acute and chronic hemolysis, as well as counter the adverse effects associated with Hb-based oxygen therapeutics.

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“…48 Several studies have shown that the antioxidant ␣-tocopherol inhibits platelet aggregation. 31,49,50 Nitrosothiols have also been shown to inhibit platelet aggregation.…”

Section: Duffy Et Al Tea Effects On Platelet Aggregationmentioning

confidence: 99%

Effect of Acute and Chronic Tea Consumption on Platelet Aggregation in Patients With Coronary Artery Disease

Duffy

Vita

Holbrook

et al. 2001

ATVB

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Abstract-Epidemiological studies suggest that tea consumption is associated with a decreased risk of cardiovascular events, but the mechanisms of benefit remain undefined. Platelet aggregation is a precipitating event in cardiovascular disease, and tea contains antioxidant flavonoids that are known to decrease platelet aggregation in vitro. To test the effect of tea consumption on platelet aggregation, we randomized 49 patients with coronary artery disease to either 450 mL of black tea or water consumed initially, followed by 900 mL of tea or water daily for 4 weeks in a crossover design. Ex vivo platelet aggregation in platelet-rich plasma was assessed in response to ADP and thrombin receptor-activating peptide at baseline and 2 hours and 4 weeks after beverage consumption. We observed dose-dependent platelet aggregation in response to each agonist, and neither relation was altered by acute or chronic tea consumption. Plasma flavonoids increased with acute and chronic tea consumption, indicating adequate absorption of tea flavonoids. In conclusion, these results demonstrate that acute and chronic black tea consumption does not affect ex vivo platelet aggregation in patients with coronary artery disease. These findings suggest that an effect of tea flavonoids on platelet aggregation is unlikely to be the explanation for the reduction in risk of cardiovascular events noted in epidemiological studies. Key Words: platelet aggregation Ⅲ tea Ⅲ flavonoids Ⅲ coronary artery disease R ecent epidemiological studies strongly suggest an inverse relationship between tea consumption and cardiovascular disease risk, 1-5 with 1 notable exception. 6 There is also convincing evidence that dietary intake of antioxidant flavonoids from tea and other sources (eg, red wine, onions, apples, and broccoli) is associated with reduced cardiovascular risk. [1][2][3][4][5][7][8][9] The benefit of high flavonoid intake may be greater for individuals with established coronary artery disease (CAD), 1,10 although favorable effects have also been demonstrated in people without evidence of atherosclerosis. 5,8,9 One proposed mechanism for the apparent benefit of tea and other sources of flavonoids is their favorable effect on platelet aggregation. [11][12][13][14][15][16] These polyphenols may inhibit platelet aggregation by a number of different mechanisms, including inhibition of lipoxygenase, cyclooxygenase, 13,17 cAMP phosphodiesterase, 12,18 and cGMP phosphodiesterase. 19 Other platelet-inhibitory effects of flavonoids include thromboxane receptor antagonism, 15 scavenging of reactive oxygen species such as superoxide anion, 20 decreasing phospholipase C activation by blunting hydrogen peroxide production, 21 and inhibition of lipid peroxidation. 14 Flavonoids also enhance nitric oxide (NO) production from the endothelium. 22 NO is a potent inhibitor of platelet adhesion, aggregation, [23][24][25] and thrombosis, 26 and impaired platelet production of NO has been associated with acute coronary syndromes. 27 A recent study demonstrated dose-...

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Enhancement of platelet function by superoxide anion.

Cited by 177 publications

References 27 publications

Myeloperoxidase-Mediated Platelet Release Reaction

Myeloperoxidase-Mediated Platelet Release Reaction

Sequestration of extracellular hemoglobin within a haptoglobin complex decreases its hypertensive and oxidative effects in dogs and guinea pigs

Effect of Acute and Chronic Tea Consumption on Platelet Aggregation in Patients With Coronary Artery Disease

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