Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0220723 (PCA)
 4,687 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. This study examines whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in patients with coronary artery disease (CAD). In a randomized prospective, double-blind, crossover, and placebo-controlled study, 42 patients with CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800 to 1,200 mg/day) or placebo for 3 months (phase 1) followed by a 4-week wash-out period, and the crossover treatment for 3 months (phase 2). PDT, platelet aggregation, platelet P-selectin flow cytometry, monocyte tissue factor procoagulant activity (TF-PCA), and adhesion molecule density were assessed before and after each phase. PDT was evaluated by an ex vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35% in patients who received magnesium versus placebo (delta change from baseline -24 vs 26 mm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA, or adhesion molecules. Oral magnesium treatment inhibited PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.
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PMID:Oral magnesium supplementation inhibits platelet-dependent thrombosis in patients with coronary artery disease. 1042 31

The use of magnesium in the treatment of acute myocardial infarction remains controversial despite preliminary experimental evidence that magnesium plays a beneficial role as a regulator of thrombosis. The aim of our study was to determine whether oral magnesium treatment inhibits platelet-dependent thrombosis (PDT) in stable patients with coronary artery disease (CAD). In a randomized prospective, double-blind, cross-over and placebo controlled study, 42 patients with stable CAD (37 men, 5 women, mean age 68 +/- 9 years) on aspirin received either magnesium oxide tablets (800-1,200 mg/day) or placebo for 3 months (Phase 1) followed by a 4-week washout period, and the cross-over treatment for 3 months (Phase 2). PDT, platelet aggregation, platelet P-selectin flow-cytometry, monocyte tissue factor procoagulant activity (TF-PCA) and adhesion molecules density were assessed before and after each phase. PDT was evaluated by an ex-vivo perfusion model using the Badimon chamber. Median PDT was significantly reduced by 35 percent in patients who received magnesium versus placebo (D change from baseline: -24 vs. 26 microm2/mm; p = 0.02, respectively). There was no significant effect of magnesium treatment on platelet aggregation, P-selectin expression, monocyte TF-PCA or adhesion molecules. Oral magnesium treatment inhibits PDT in patients with stable CAD. This effect appears to be independent of platelet aggregation or P-selectin expression, and is evident despite aspirin therapy. These findings suggest a potential mechanism whereby magnesium may beneficially alter outcomes in patients with CAD.
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PMID:Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart disease patients. 1115 97

Tissue factor (TF) is the physiological initiating mechanism for blood coagulation. Platelets play an important role in monocyte TF expression, thrombosis and inflammation. Aspirin, clopidogrel and cilostazol, which inhibit platelet responses by different mechanisms, are widely used in patients with arterial diseases. We tested the hypothesis that platelet-inhibiting agents inhibit the levels of circulating TF procoagulant activity (TF-PCA) in patients with peripheral arterial disease (PAD). Twenty-six patients with lower extremity PAD, average age 65.9 +/- 8.4 years (mean +/- SEM), were studied at baseline and following sequential two-week treatment regimens with aspirin (325 mg daily), clopidogrel (75 mg daily) or a phosphodiesterase inhibitor cilostazol (100 mg twice daily) singly, and with each possible combination of these agents. Circulating TF-PCA in whole blood, and plasma factor VIIa, prothrombin fragment F1.2, thrombin-antithrombin complexes (TAT), and P-selectin were measured. Baseline TF-PCA levels in the patients were elevated (131 +/- 19 U/ml) compared to control subjects (23 +/- 2, p < 0.0001). TF-PCA levels declined following treatment with clopidogrel alone, and with combinations of clopidogrel with aspirin or cilostazol, with the lowest levels being with the triple-drug combination. Plasma P-selectin declined in all treatment groups. No changes were noted in plasma factor VIIa, F1.2 or TAT. In conclusion, treatment of PAD patients with antiplatelet agents decreases circulating TF, a molecule with prothrombotic and proinflammatory effects. These findings suggest an unrecognized mechanism, beyond inhibiting aggregation responses, for the efficacy of antiplatelet drugs in patients with arterial diseases.
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PMID:Effect of antiplatelet agents clopidogrel, aspirin, and cilostazol on circulating tissue factor procoagulant activity in patients with peripheral arterial disease. 1713 67

Platelets have a major role in clotting activation and contribute to the innate immune response during systemic infections. Human platelets contain tissue factor (TF) and express functional Toll-like receptor 4 (TLR4). However, the role of TLR4 in triggering the procoagulant properties of platelets, upon challenge with bacteria, is yet unknown. Our hypothesis is that E. coli O111-TLR4 interaction activates platelets and elicits their procoagulant activity. We demonstrated that the strain, but not ultrapure LPS, increased surface P-selectin expression, platelet dependent TF procoagulant activity (TF-PCA) and prompted a faster thrombin generation (TG). Blockade of TLR4 resulted in decreased platelet activation, TF-PCA and TG, revealing the participation of this immune receptor on the procoagulant response of platelets. Our results provide a novel mechanism by which individuals with bacterial infections would have an increased incidence of blood clots. Furthermore, the identification of platelet TF and TLR4 as regulators of the effect of E. coli O111 might represent a novel therapeutic target to reduce the devastating consequences of the hemostatic disorder during sepsis.
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PMID:Human platelet interaction with E. coli O111 promotes tissue-factor-dependent procoagulant activity, involving Toll like receptor 4. 2895 60