Increased levels of circulating microparticles in patients with severe aortic valve stenosis
Increased levels of circulating microparticles in patients with severe aortic valve stenosis
复制标题
DOI：
10.1160/th07-05-0334
复制
发表时间：
2008-04-01
影响因子：
6.7
通讯作者：
Moser, Martin
中科院分区：
文献类型：
--
作者：
Diehl, Philipp;Nagy, Ferenc;Moser, Martin
主动脉瓣狭窄进展的机制尚不清楚。病理标本分析表明涉及单核细胞和慢性全身炎症。我们假设主动脉口收缩引起的剪切应力通过激活循环血细胞从而产生微粒而导致全身促炎症。使用流式细胞术，我们分析了 22 名严重主动脉瓣狭窄 (AVS) 患者和 18 名对照患者，了解血小板（PMP：CD31（+）/CD61（+）或 CD62P（+））、白细胞（LMP：CDIIb（+））和内皮细胞（EMP：CD62E（+））来源的循环微粒的生成。除了收缩的阀门孔口之外，组是相似的。 AVS 患者的 PMP 增加，其数量与瓣膜剪切应力相关。 AVS 患者的单核细胞被激活，LMP 数量的增加和 PMP-单核细胞缀合物的检测也反映了这一观察结果。此外，在 AVS 患者中，反映内皮细胞激活但也赋予全身炎症活性的 EMP 增加，并且与激活的单核细胞数量相关。总之，我们表明 AVS 伴随着微粒水平的增加，并且剪切应力可以诱导微粒的形成。根据我们的结果和其他研究人员的组织学发现，与主动脉瓣狭窄相关的剪切应力会诱发恶性循环，包括 PMP 的产生、随后单核细胞和 LMP 的激活以及最终导致主动脉瓣狭窄进展的内皮细胞的激活，这似乎是合理的。
The mechanisms of the progression of aortic valve stenosis are unknown. The involvement of mononuclear cells and of chronic systemic inflammation has been suggested by analysis of pathological specimens. We hypothesize that shear stress caused by the constricted aortic orifice contributes to systemic proinflammation by activation of circulating blood cells and thereby generation of microparticles. Using flow cytometry we analyzed 22 patients with severe aortic valve stenosis (AVS) and 18 patient controls for the generation of circulating microparticles from platelet- (PMPs: CD31(+)/CD61(+) or CD62P(+)), leukocyte- (LMPs: CDIIb(+)) and endothelial cell (EMPs: CD62E(+)) origin. Apart from the constricted valve orifice groups were similar. PMPs were increased in AVS patients and their number correlated with valvular shear stress. Monocytes were activated in AVS patients, an observation that was also reflected by increased numbers of LMPs and by the detection of PMP-monocyte conjugates. Furthermore, EMPs reflecting the activation of endothelial cells but also conferring systemic inflammatory activity were increased in AVS patients and correlated with the number of activated monocytes. In conclusion, we show that AVS is accompanied by increased levels of microparticles and that shear stress can induce the formation of microparticles. Based on our results and histologic findings of other investigators the speculation that shear stress related to aortic valve stenosis induces a vicious circle including the generation of PMPs, the subsequent activation of monocytes and LMPs and finally the activation of endothelial cells contributing to the progress of aortic valve stenosis appears to be justified.