Platelet Aggregation and Vasoconstriction Related to Platelet Cyclooxygenase and 12-Lipoxygenase Pathways

Abstract

Many thrombotic angiopathies originate as a result of an abnormal interaction between platelets and blood vessel walls. The present study focused on the platelet activating factor (PAF)-induced platelet aggregation mechanism and was undertaken to clarify the association between platelet aggregation and vasocontractility. Vasoconstriction was examined in perfused artery segments dissected from the central ear artery of male rabbits. Autologous platelet rich plasma (PRP) was infused into the perfusion system. Vasocontractility was examined in response to PRP plus PAF or collagen. The vasocontractile response to noradrenaline (NA-R) on perfusion of PRP plus PAF was initially augmented, then gradually attenuated. The platelet aggregation in response to PAF was constant and longlasting and moderately inhibited by nordihydroguaiaretic acid, a 12-lipoxygenase (LOX) inhibitor, but was unaffected by indomethacin, a cyclooxygenase inhibitor. The attenuated responses disappeared and NA-R was returned to the initial level on pretreatment with tetrodotoxin which excluded neurogenic components from the arterial preparation. In contrast, a repetitive NA-R to PRP plus collagen gradually increased. Thus, it may be concluded that PAFinduced platelet aggregation participates in activation of the 12-LOX pathway and is accompanied by the release of vasodepressor nerve-stimulating substances from platelets. J Atheroscler Thromb, 2005; 12: 154-162.

Plasma Level of Platelet-Derived Microparticles Is Associated with Coronary Heart Disease Risk Score in Healthy Men

“…PDMPs reportedly play a pivotal role in the acute occlusion of atherosclerotic small arteries or arterioles where pathological levels of fluid shear stress can be found 1,[40][41][42] . Clinically, elevated levels of plasma PDMP are associated with thrombotic disorders 12,18,27,30) .…”

Is There a Rationale for Antiplatelet Therapy in Acute Heart Failure?

“…In contrast, conflicting data have been observed with regard to the association of platelet biomarkers with prognosis. 7,9,21,23,24 Notably, the small size of these previous studies underscores the need for ongoing exploration of the biology of platelet activation in HF. n/a n/a n/a n/a Kandis et al 10 Acute vs chronic HF Acute>chronic HF Yes n/a n/a n/a n/a n/a n/a n/a No differences between groups; decrease at followup for acute HF n/a n/a n/a n/a …”

“…In fact, the platelet response to agonists, such as ADP, involves not only platelet aggregation but also secretion of several vasoactive agents, such as serotonin and thromboxane A2. 7 Animal models have demonstrated that these substances cause vasoconstriction and further promote platelet aggregation.…”

“…5 Endothelial damage and dysfunction along with imbalances in nitric oxide production and increased expression of adhesion molecules may lead to enhanced platelet adhesion and activation. 7,29 In addition, increased levels of angiotensin II and circulating catecholamines, 7,8 oxidative stress, and inflammation 30,31 contribute to the increased activity of platelets and the coagulation cascade. 16 Although these mechanisms can lead to platelet activation, the extent to which this activation may play a direct role in the pathophysiology of AHF remains unclear.…”

“…One such potential mechanism is platelet activation. 5,6 The activation of neurohormonal, inflammatory, and thrombotic pathways [7][8][9] is known to be associated with enhanced platelet reactivity in AHF. [10][11][12][13][14] However, whether increased platelet activity is simply a marker of this systemic imbalance or an actual contributor to acute decompensation is incompletely understood.…”