Tremblay Joshua C, Thom Stephen R, Yang Ming, Ainslie Philip N
Centre for Heart, Lung, and Vascular Health School of Health and Exercise Science, University of British Columbia, Kelowna, Canada.
Department of Emergency Medicine, University of Maryland, Baltimore, USA.
Atherosclerosis. 2017 Jan;256:115-122. doi: 10.1016/j.atherosclerosis.2016.12.004. Epub 2016 Dec 2.
Exposing the endothelium to acute periods of imposed oscillatory shear stress reduces endothelial function and elevates circulating microparticles (MPs). Oscillatory shear stress may be especially pathogenic when superimposed on hypoxia, an environmental stimulus that disrupts the endothelial milieu. We examined the effects of acute manipulation of oscillatory shear stress on endothelial function and circulating MPs at sea level (SL) and high altitude (HA).
Healthy adults (n = 12) participated, once at SL and once on the second or third day at HA (3800 m). Oscillatory shear stress was provoked using a 30-min distal cuff occlusion intervention (75 mmHg). Endothelial function was assessed before and immediately after the intervention in the brachial artery by reactive hyperaemia flow-mediated dilatation (FMD). Venous blood samples of MPs (flow cytometry) were obtained before and during the last five minutes of the shear intervention.
At baseline, circulating MPs were two-fold higher at HA (p = 0.011) and brachial artery diameter was constricted (p = 0.015). Although the intervention at SL increased endothelial-derived MPs by 83 ± 39% (mean ± SEM; p = 0.021), FMD was unaltered. Conversely, at HA, the intervention elicited a 26 ± 11% reduction in FMD (p = 0.020); this reduction was inversely correlated with the change in total circulating MPs (r = -0.737, p = 0.006) and the change in endothelial-derived MPs (r = -0.614, p = 0.034).
The vascular endothelium appears to be susceptible to periods of oscillatory shear stress at HA, where impairments in endothelium-dependent vasodilatation may be amplified by endothelial injury. These findings have important implications for understanding the early impact of clinical situations of hypoxaemia on the vascular endothelium.
使内皮细胞暴露于急性施加的振荡剪切应力环境中会降低内皮功能并增加循环微粒（MPs）。当振荡剪切应力叠加在缺氧这种破坏内皮环境的环境刺激因素上时，其致病性可能会更强。我们研究了急性改变振荡剪切应力对海平面（SL）和高海拔（HA）地区内皮功能及循环MPs的影响。
12名健康成年人参与研究，他们在海平面进行了一次实验，在高海拔地区（3800米）的第二天或第三天又进行了一次实验。通过30分钟的远端袖带闭塞干预（75mmHg）来引发振荡剪切应力。在干预前后，通过反应性充血血流介导的血管舒张（FMD）评估肱动脉的内皮功能。在剪切干预的最后五分钟内及干预前采集静脉血样本检测MPs（流式细胞术）。
在基线时，高海拔地区循环MPs水平高出两倍（p = 0.011），肱动脉直径收缩（p = 0.015）。虽然在海平面进行干预使内皮源性MPs增加了83±39%（平均值±标准误；p = 0.021），但FMD未改变。相反，在高海拔地区，干预使FMD降低了26±11%（p = 0.020）；这种降低与总循环MPs的变化呈负相关（r = -0.737，p = 0.006），与内皮源性MPs的变化也呈负相关（r = -0.614，p = 0.034）。
在高海拔地区，血管内皮似乎对振荡剪切应力环境敏感，在该环境下，内皮依赖性血管舒张功能的损害可能会因内皮损伤而加剧。这些发现对于理解低氧血症临床情况对血管内皮的早期影响具有重要意义。
