LUNAM Université, Angers, France ; INSERM, U1063, Angers, France.
PLoS One. 2013 Sep 3;8(9):e73088. doi: 10.1371/journal.pone.0073088. eCollection 2013.
Microparticles (MPs) are small vesicles released during cell activation or apoptosis. They are involved in coagulation, inflammation and vascular dysfunction in several diseases. We characterized circulating MPs from Crohn's Disease (CD) patients and evaluated their effects on endothelial function and vascular reactivity after in vivo injection into mice.
Circulating MPs and their cellular origins were examined by flow cytometry from blood samples from healthy subjects (HS) and inactive or active CD patients. MPs were intravenously injected into mice. After 24 hours, endothelial function and vascular reactivity were assessed.
Circulating MP levels did not differ between HS and inactive CD patients except for an increase in leukocyte-derived MPs in CD. Active CD patients compared to HS displayed increased total circulating MPs, pro-coagulant MPs and those from platelets, endothelium, erythrocytes, leukocytes, activated leukocytes and activated platelets. A significant correlation was found between total levels of MPs, those from platelets and endothelial cells, and the Harvey-Bradshaw clinical activity index. MPs from CD, but not from HS, impaired endothelium-dependent relaxation in mice aorta and flow-induced dilation in mice small mesenteric arteries, MPs from inactive CD patients being more effective than those from active patients. CDMPs induced vascular hypo-reactivity in aorta that was prevented by a nitric oxide (NO)-synthase inhibitor, and was associated with a subtle alteration of the balance between NO, reactive oxygen species and the release of COX metabolites.
We provide evidence that MPs from CD patients significantly alter endothelial and vascular function and therefore, may play a role in CD pathophysiology, at least by contributing to uncontrolled vascular-dependent intestinal damage.
微粒（MPs）是细胞激活或凋亡过程中释放的小囊泡。它们参与多种疾病中的凝血、炎症和血管功能障碍。我们对克罗恩病（CD）患者的循环 MPs 进行了特征描述，并评估了它们在体内注射到小鼠体内后对内皮功能和血管反应性的影响。
通过流式细胞术检测来自健康受试者（HS）和非活动或活动 CD 患者血液样本中的循环 MPs 及其细胞来源。将 MPs 静脉内注射到小鼠体内。24 小时后，评估内皮功能和血管反应性。
除了 CD 中白细胞来源的 MPs 增加外，HS 和非活动 CD 患者之间的循环 MPs 水平没有差异。与 HS 相比，活动 CD 患者显示出总循环 MPs、促凝 MPs 以及来自血小板、内皮细胞、红细胞、白细胞、活化白细胞和活化血小板的 MPs 增加。发现 MPs 的总水平、来自血小板和内皮细胞的 MPs 与 Harvey-Bradshaw 临床活动指数之间存在显著相关性。来自 CD 的 MPs，但不是来自 HS 的 MPs，损害了小鼠主动脉中的内皮依赖性松弛和小鼠小肠系膜动脉中的血流诱导扩张，来自非活动 CD 患者的 MPs 比来自活动患者的 MPs 更有效。CDMPs 诱导了主动脉的血管低反应性，这可以被一氧化氮（NO）-合酶抑制剂预防，并且与 NO、活性氧物质和 COX 代谢物释放之间的平衡的细微改变有关。
我们提供的证据表明，来自 CD 患者的 MPs 显著改变了内皮和血管功能，因此，可能在 CD 的病理生理学中发挥作用，至少通过有助于不受控制的血管依赖性肠道损伤。
