Abstract
Hypertension is known to be associated with platelet overactivity, but the direct effects of hydrostatic pressure on platelet function remain unclear. The present study sought to investigate whether elevated hydrostatic pressure is responsible for platelet activation and to address the potential role of peroxisome proliferator-activated receptor-γ (PPARγ). We observed that hypertensive patients had significantly higher platelet volume and rate of ADP-induced platelets aggregation compared to the controls. In vitro, Primary human platelets were cultured under standard (0 mmHg) or increased (120, 180, 240 mmHg) hydrostatic pressure for 18 h. Exposure to elevated pressure was associated with morphological changes in platelets. Platelet aggregation and PAC-1 (the active confirmation of GPIIb/IIIa) binding were increased, CD40L was translocated from cytoplasm to the surface of platelet and soluble CD40L (sCD40L) was released into the medium in response to elevated hydrostatic pressure (180 and 240 mmHg). The PPARγ activity was up-regulated as the pressure was increased from 120 mmHg to 180 mmHg. Pressure-induced platelet aggregation, PAC-1 binding, and translocation and release of CD40L were all attenuated by the PPARγ agonist Thiazolidinediones (TZDs). These results demonstrate that platelet activation and aggregation are increased by exposure to elevated pressure and that PPARγ may modulate platelet activation induced by high hydrostatic pressure.
Highlights
The relationship between hypertension and platelet function is a subject of increasing interest
We examined several specific parameters relating to volume (MPV), width (PDW) and the platelet-large cell ratio (PLCR) as a function of hydrostatic pressure
Exposure to elevated pressure was accompanied by up-regulation of the activity of peroxisome proliferator-activated receptor-c (PPARc), and a specific PPARc agonist was able to prevent platelet activation, suggesting that the up-regulation of PPARc under high pressure conditions is likely to attenuate the adverse effects of elevated hydrostatic pressure
Summary
The relationship between hypertension and platelet function is a subject of increasing interest. Recent research have revealed that both platelet clumping and cohesion are sthenic in patients with hypertension [1,2], and indices of platelet function including platelet size, aggregation and the release of platelet activation markers are all increased in subjects with hypertension [3]. Platelet activation is accompanied by a marked increase in the membrane levels of glycoproteins (GP) IIb/IIIa, and receptor–ligand interactions between these molecules contribute to platelet aggregation [4,5]. The role of platelets in inflammation is thought to be mediated through CD40 ligand (CD40L)–CD40 interactions. Besides a membrane-bound form, CD40L exists as a soluble molecule; soluble CD40L (sCD40L), mainly derives from activated platelets and T cells after stimulation [10,11]. The role of blood pressure in platelet aggregation, immunoregulation and inflammation remains unclear, despite abundant evidence that increased blood pressure can lead to functional impairment of platelets, and the intracellular pathways involved remain obscure
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