Doroudi R, Gan L M, Selin Sjögren L, Jern S
Clinical Experimental Research Laboratory, Heart and Lung Institute, Sahlgrenska University Hospital/Ostra, Göteborg University, Göteborg, Sweden.
Biochem Biophys Res Commun. 2000 Mar 5;269(1):257-64. doi: 10.1006/bbrc.2000.2279.
This study investigated the effects of shear stress on gene expression of prostacyclin synthesis-related enzymes cyclooxygenases (COX-1 and COX-2), prostacyclin synthase (PGS), and thromboxane synthase (TXS) and their metabolites prostaglandin (PGI(2)) and thromboxane A(2) (TXA(2)) in endothelium of intact conduit vessels. Paired human umbilical veins were perfused at high/low shear stress (25/<4 dyn/cm(2)) at identical intraluminal pressure (20 mmHg) for 1.5, 3, or 6 hours in a computerized vascular model. High shear perfusion induced a significant, monophasic upregulation of PGS and TXS gene expressions after 6 hours. COX-1 and COX-2 mRNA showed a biphasic response with peaks at 1.5 and 6 hours, with a nadir level at 3 hours. Shear-induced gene expression was associated with a significantly greater accumulation of 6-keto prostaglandin F(1alpha) and TXA(2) in the perfusion medium. Thus, shear stress independently of perfusion pressure alters the expression of prostacyclin synthesis-related enzymes and the biosynthesis of their vasoactive metabolites.
本研究调查了剪切应力对完整导管血管内皮中前列环素合成相关酶环氧化酶（COX-1和COX-2）、前列环素合酶（PGS）和血栓素合酶（TXS）及其代谢产物前列腺素（PGI₂）和血栓素A₂（TXA₂）基因表达的影响。在计算机化血管模型中，将配对的人脐静脉在相同的管腔内压力（20 mmHg）下以高/低剪切应力（25/<4 dyn/cm²）灌注1.5、3或6小时。高剪切力灌注6小时后，PGS和TXS基因表达出现显著的单相上调。COX-1和COX-2 mRNA表现出双相反应，在1.5小时和6小时出现峰值，在3小时达到最低点。剪切诱导的基因表达与灌注介质中6-酮前列腺素F₁α和TXA₂的显著积累有关。因此，独立于灌注压力的剪切应力改变了前列环素合成相关酶的表达及其血管活性代谢产物的生物合成。
