Ulfhammer Erik, Ridderstråle Wilhelm, Andersson Maria, Karlsson Lena, Hrafnkelsdóttir Thórdís, Jern Sverker
Clinical Experimental Research Laboratory, Sahlgrenska University Hospital/Ostra, the Cardiovascular Institute, Göteborg University, Göteborg, Sweden.
J Hypertens. 2005 Aug;23(8):1551-7. doi: 10.1097/01.hjh.0000175931.71150.02.
We previously reported that patients with primary hypertension have an impaired ability to release tissue-type plasminogen activator acutely from the vascular endothelium, and recently found that lowering blood pressure can restore this capacity. We hypothesized that the suppression of the fibrinolytic system is caused by the chronic pressure-induced increased haemodynamic load on the endothelium.
This study investigated the effect of the tensile force component of blood pressure by exposing cultured human aortic endothelial cells to 10% cyclic strain for 6-72 h. Messenger RNA levels of tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1 were analysed using Taqman real-time reverse transcriptase-polymerase chain reaction and protein release by enzyme-linked immunosorbent assay.
Tensile stimulation resulted in a transient initial upregulation of tissue-type plasminogen activator mRNA at 6 h (53%), which declined with time, and at 48 h had switched to a 28% downregulation. The reduction was sustained after 72 h. Tissue-type plasminogen activator protein secretion showed a similar but somewhat delayed response, with a transient increase in release at 6 h (60%), declining to a final 12% reduction at 72 h. A similar pattern was observed for urokinase-type plasminogen activator mRNA. By contrast, plasminogen activator inhibitor 1 mRNA expression and protein secretion increased at all timepoints (16-47%).
Prolonged tensile stimulation impairs fibrinolytic activity in human aortic endothelial cells by a dual action, with suppression of plasminogen activator expression and increased inhibitor production. This effect of tensile stress may contribute to the reduced fibrinolytic capacity observed in patients with hypertension.
我们之前报道过，原发性高血压患者急性释放血管内皮组织型纤溶酶原激活物的能力受损，最近发现降低血压可恢复这种能力。我们推测纤溶系统的抑制是由慢性压力引起的内皮血流动力学负荷增加所致。
本研究通过将培养的人主动脉内皮细胞暴露于10%的循环应变6 - 72小时，研究血压张力成分的作用。使用Taqman实时逆转录聚合酶链反应分析组织型纤溶酶原激活物、尿激酶型纤溶酶原激活物和纤溶酶原激活物抑制剂1的信使核糖核酸水平，并通过酶联免疫吸附测定分析蛋白质释放情况。
拉伸刺激导致组织型纤溶酶原激活物信使核糖核酸在6小时时短暂初始上调（53%），随后随时间下降，在48小时时转变为下调28%。72小时后这种降低持续存在。组织型纤溶酶原激活物蛋白分泌表现出类似但稍有延迟的反应，在6小时时释放短暂增加（60%），在72小时时最终下降12%。尿激酶型纤溶酶原激活物信使核糖核酸也观察到类似模式。相比之下，纤溶酶原激活物抑制剂1信使核糖核酸表达和蛋白分泌在所有时间点均增加（16 - 47%）。
长时间拉伸刺激通过双重作用损害人主动脉内皮细胞的纤溶活性，抑制纤溶酶原激活物表达并增加抑制剂产生。这种拉伸应力的作用可能导致高血压患者纤溶能力降低。
