[Thrombosis and coronary disease: neutrophils, nitric oxide and aspirin].
In recent years, relevant changes have occurred in the knowledge of the cellular mechanisms regulating platelet aggregation and adhesion to the endothelial surface. In particular, major aspects of the interactions between platelets and endothelial cells and neutrophils have been clarified. These interactions involve not only thrombosis-promoting or thrombosis-inhibiting properties but also several aspects of the regulation of vascular function. A new concept has progressively emerged showing thrombosis as a multicellular event in which cell-to cell interactions between platelets, neutrophils, and endothelium regulate the size of a growing thrombus. In brief, there is consistent evidence showing that two vasodilating mediators produced by endothelial cells and neutrophils (nitric oxide and prostacyclin) have antiaggregating platelet effects. Platelet activation is particularly relevant in myocardial ischemia, and several pharmacological strategies have been devised to prevent intravascular platelet activation. Aspirin remains a keystone of these preventive and damage-limiting strategies. Current knowledge maintains that low doses of aspirin decrease in vivo platelet aggregation by a selective inhibitory effect on thromboxane A2 production by platelets with maintenance of prostacyclin production by the endothelium. We have recently focussed our research on the basis that the antiaggregating effect of aspirin could be explained not only by the above-mentioned effects on thromboxane A2 synthesis, but also through its action on neutrophils. Our in vitro and ex vivo studies have demonstrated that neutrophils enhance the antiaggregating effects of acetylsalicilic acid on platelets. We have shown that acetylsalicilic acid stimulates nitric oxide production on neutrophils inhibiting the aggregating effects of thrombin, ADP or epinephrine on platelets. the role of the neutrophils in ischemic events enhancing the tissue damage through the release of several proteases, reactive oxygen species and tumor necrosis factor-alpha has been extensively demonstrated. In an experimental model of acute ischemia/reperfusion in rabbits, we have shown that acetylsalicilic acid is able to enhance the nitric oxide production by neutrophils providing a potential mechanism for the beneficial action of aspirin in the myocardial infarction. Further research is needed to assess the mechanisms of the action of aspirin during the thrombotic phenomena and its effects on the different types of cells that compound the microvascular environment.
López-Farré
A
A
Laboratorio de Nefrología, Hipertensión e Investigación Cardiovascular, Fundación Jiménez Díaz, Madrid.
Farré
J
J
Sánchez de Miguel
L
L
Romero
J
J
Gómez
J
J
Rico
L
L
Casado
S
S
D001241:Aspirin / Q000627:therapeutic use*; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D006801:Humans; D009504:Neutrophils / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D013927:Thrombosis / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control
D010975:Platelet Aggregation Inhibitors; D009569:Nitric Oxide; D001241:Aspirin
Trombosis y enfermedad coronaria: neutrófilos, óxido nítrico y aspirina.