Rao Fang, Yang Ren-Qiang, Chen Xiao-Shu, Xu Jin-Song, Fu Hui-Min, Su Hai, Wang Ling
Department of Cardiology, Guangdong General Hospital, Guangzhou, PR China ; Guangdong Academy of Medical Sciences, Guangzhou, PR China.
Department of Cardiology, The second affiliated hospital of Nanchang University, Nanchang, PR China.
PLoS One. 2014 Feb 28;9(2):e89654. doi: 10.1371/journal.pone.0089654. eCollection 2014.
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.
高血压与血小板过度活跃有关，但流体静压对血小板功能的直接影响仍不清楚。本研究旨在探讨流体静压升高是否导致血小板活化，并探讨过氧化物酶体增殖物激活受体γ（PPARγ）的潜在作用。我们观察到，与对照组相比，高血压患者的血小板体积和ADP诱导的血小板聚集率显著更高。在体外，将原代人血小板在标准（0 mmHg）或升高（120、180、240 mmHg）的流体静压下培养18小时。暴露于升高的压力与血小板的形态变化有关。响应于升高的流体静压（180和240 mmHg），血小板聚集和PAC-1（GPIIb/IIIa的活性形式）结合增加，CD40L从细胞质转运到血小板表面，可溶性CD40L（sCD40L）释放到培养基中。随着压力从120 mmHg增加到180 mmHg，PPARγ活性上调。PPARγ激动剂噻唑烷二酮（TZDs）减弱了压力诱导的血小板聚集、PAC-1结合以及CD40L的转运和释放。这些结果表明，暴露于升高的压力会增加血小板活化和聚集，并且PPARγ可能调节高流体静压诱导的血小板活化。
