Frequency and severity of cyclic flow alternations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury.

Abstract

Frequency and severity of cyclic flow alternations and platelet aggregation predict the severity of neointimal proliferation following experimental coronary stenosis and endothelial injury ( ABSTRACTThe role of recurrent platelet aggregation in the development of neointimal proliferation of coronary arteries was explored in this study, and the hypothesis was evaluated that recurrent platelet aggregation and the consequent frequency and severity of cyclic coronary blood flow variations are important pathophysiologic factors in the subsequent development of neointimal proliferation. In 24 chronically instrumented dogs, variable degrees of coronary artery neointimal proliferation were observed 3 weeks after mechanical i jury of the arterial endothelium and the placement of an external coronary artery constrictor. The severity of neointimal proliferation at 21 days was closely related to the frequency and severity of cyclic coronary blood flow variations during the initial 7 days after instrumentation of the animals, itself a manifestation of recurrent platelet aggregation and dislodgement. Pharmacological therapy with a dual thromboxane A2 synthetase inhibitor and receptor antagonist and with a serotonin S2 receptor antagonist frequently was successful in abolishing cyclic blood flow variations and in retarding neointimal proliferation.

Local gene transfer of tissue factor pathway inhibitor regulates intimal hyperplasia in atherosclerotic arteries

“…However, previous studies (25,27) have shown that adenoviral gene transfer of TFPI exerts significant protection against the development of cyclic flow reductions, in accordance with reports that administration of recombinant TFPI markedly reduced the procoagulant properties of balloon-injured rabbit arteries (32,33). We therefore speculate that local gene transfer of TFPI may prevent intimal hyperplasia, at least in part, by decreasing the local burden of thrombusdependent growth factors (3,4).…”

“…The pathogenesis of intimal hyperplasia after vascular injury is believed to involve diverse signaling cascades that ultimately converge on vascular smooth muscle cells (VSMC), stimulating their proliferation and migration and their prolonged secretion of extracellular matrix (1,2). Thrombus formation at the site of injury contributes to reobstruction of the vessel through its bulk and through the release of growth and chemotactic factors that further promote accumulation of intimal VSMC (1)(2)(3). Proteins involved in blood clotting, including the tissue factor (TF)͞fac-tor VIIa complex, factor Xa, and thrombin (4-6), exert chemotactic and mitogenic activity on VSMC and other cells.…”

Intracoronary Thrombus and Platelet Glycoprotein IIb/IIIa Receptor Blockade With Tirofiban in Unstable Angina or Non–Q-Wave Myocardial Infarction

“…Plaque passivation could be explained by better dissolution of the thrombus, which is by itself a powerful thrombogenic stimulus. 13 Additional mechanisms could be prevention of the release of platelet-active products associated with cell proliferation 27 and prevention of platelet-leukocyte interaction. 28 The impaired outcome associated with persistence of thrombus has important implications for patient management.…”

Ativação plaquetária em formas clínicas distintas da doença arterial coronariana (papel da P-selectina e de outros marcadores nas anginas estável e instável)

“…Serotonin -Clinical studies [28][29][30] artery stenosis and endothelial injury. Activated platelets release serotonin in substantial quantities causing vasoconstriction and recurrent aggregation of platelets with cyclic flow reductions.…”