Center for Molecular and Vascular Biology, University of Leuven, Belgium.
Thromb Haemost. 2012 Oct;108(4):756-68. doi: 10.1160/TH12-03-0161. Epub 2012 Aug 7.
Epidemiological studies indicate that elderly persons are particularly susceptible to the cardiovascular health complications of air pollution, but pathophysiological mechanisms behind the increased susceptibility remain unclear. Therefore, we investigated how continuous traffic-related air pollution exposure affects haemostasis parameters in young and old mice. Young (10 weeks) and old (20 months) mice were placed in an urban roadside tunnel or in a clean environment for 25 or 26 days and markers of inflammation and endothelial cells or blood platelet activation were measured, respectively. Plasma microvesicles and pro/anticoagulant factors were analysed, and thrombin generation analysis was performed. Despite elevated macrophage carbon load, tunnel mice showed no overt pulmonary or systemic inflammation, yet manifested reduced pulmonary thrombomudulin expression and elevated endothelial von Willebrand factor (VWF) expression in lung capillaries. In young mice, soluble P-selectin (sP-sel) increased with exposure and correlated with soluble E-selectin and VWF. Baseline plasma factor VIII (FVIII), sP-sel and VWF were higher in old mice, but did not pronouncedly increase further with exposure. Traffic-related air pollution markedly raised red blood cell and blood platelet numbers in young and old mice and procoagulant blood platelet-derived microvesicle numbers in old animals. Changes in coagulation factors and thrombin generation were mild or absent. Hence, continuous traffic-related air pollution did not trigger overt lung inflammation, yet modified pulmonary endothelial cell function and enhanced platelet activity. In old mice, subchronic exposure to polluted air raised platelet numbers, VWF, sP-sel and microvesicles to the highest values presently recorded, collectively substantiating a further elevation of thrombogenicity, already high at old age.
流行病学研究表明，老年人尤其容易受到空气污染对心血管健康的影响，但增加易感性的病理生理机制仍不清楚。因此，我们研究了持续的交通相关空气污染暴露如何影响年轻和老年小鼠的止血参数。将年轻（10 周）和老年（20 个月）小鼠分别置于城市路边隧道或清洁环境中 25 或 26 天，并分别测量炎症和内皮细胞或血小板激活标志物。分析了血浆微泡和促凝/抗凝因子，并进行了凝血酶生成分析。尽管隧道小鼠的巨噬细胞碳负荷增加，但未表现出明显的肺部或全身炎症，但其肺血栓调节蛋白表达降低，肺毛细血管内皮型 von Willebrand 因子（VWF）表达升高。在年轻小鼠中，暴露后可溶性 P 选择素（sP-sel）增加，并与可溶性 E 选择素和 VWF 相关。基线血浆因子 VIII（FVIII）、sP-sel 和 VWF 在老年小鼠中较高，但进一步暴露时不会明显增加。交通相关空气污染显著增加了年轻和老年小鼠的红细胞和血小板数量，以及老年动物的促凝性血小板衍生微泡数量。凝血因子和凝血酶生成的变化轻微或不存在。因此，持续的交通相关空气污染并未引发明显的肺部炎症，但改变了肺内皮细胞功能并增强了血小板活性。在老年小鼠中，亚慢性暴露于污染空气中会使血小板数量、VWF、sP-sel 和微泡增加到目前记录的最高值，共同证实了血栓形成的进一步升高，而这在老年时已经很高。
