CXCR4 blockade induces atherosclerosis by affecting neutrophil function.
CXCR4 blockade induces atherosclerosis by affecting neutrophil function.
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DOI：
10.1016/j.yjmcc.2014.04.021
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发表时间：
2014-09
影响因子：
5
通讯作者：
Biessen, Erik A. L.
中科院分区：
文献类型：
--
作者：
Bot, Ilze;Daissormont, Isabelle T. M. N.;Zernecke, Alma;van Puijvelde, Gijs H. M.;Kramp, Birgit;de Jager, Saskia C. A.;Sluimer, Judith C.;Manca, Marco;Herias, Veronica;Westra, Marijke M.;Bot, Martine;van Santbrink, Peter J.;van Berkel, Theo J. C.;Su, Lishan;Skjelland, Mona;Gullestad, Lars;Kuiper, Johan;Halvorsen, Bente;Aukrust, Paul;Koenen, Rory R.;Weber, Christian;Biessen, Erik A. L.
SDF-1α/CXCR 4二联体在内膜增生和早期动脉粥样硬化中起重要作用。在这里，我们试图研究其对临床相关阶段的动脉粥样硬化在小鼠和man. Immunohistochemistry分析CXCR 4在人类动脉粥样硬化病变的表达显示了一个渐进的积累CXCR 4+细胞在斑块的进展。为了阐明CXCR 4在动脉粥样硬化晚期的因果关系，我们用编码SDF-1α拮抗剂或CXCR 4降解因子的慢病毒感染的自体骨髓重建了LDLr−/−小鼠，后者影响CXCR 4的蛋白酶体降解。功能性CXCR 4阻断导致随着疾病进展斑块进行性扩张，同时也促进斑块内出血。此外，CXCR 4敲除可增加中性粒细胞的内皮粘附。与这一发现一致，抑制CXCR 4功能增加了中性粒细胞的粘附能力，减少了中性粒细胞的凋亡，并导致循环中性粒细胞的过度活化。与中性粒细胞CXCR 4在终末期动脉粥样硬化中的作用相一致，急性心血管综合征患者循环中性粒细胞CXCR 4表达降低。总之，CXCR 4通过干扰中性粒细胞功能促进斑块进展的后期阶段。
The SDF-1α/CXCR4 dyad was previously shown by us and others to be instrumental in intimal hyperplasia as well as early stage atherosclerosis. We here sought to investigate its impact on clinically relevant stages of atherosclerosis in mouse and man. Immunohistochemical analysis of CXCR4 expression in human atherosclerotic lesions revealed a progressive accumulation of CXCR4+ cells during plaque progression. To address causal involvement of CXCR4 in advanced stages of atherosclerosis we reconstituted LDLr−/− mice with autologous bone marrow infected with lentivirus encoding SDF-1α antagonist or CXCR4 degrakine, which effects proteasomal degradation of CXCR4. Functional CXCR4 blockade led to progressive plaque expansion with disease progression, while also promoting intraplaque haemorrhage. Moreover, CXCR4 knockdown was seen to augment endothelial adhesion of neutrophils. Concordant with this finding, inhibition of CXCR4 function increased adhesive capacity and reduced apoptosis of neutrophils and resulted in hyperactivation of circulating neutrophils. Compatible with a role of the neutrophil CXCR4 in end-stage atherosclerosis, CXCR4 expression by circulating neutrophils was lowered in patients with acute cardiovascular syndromes. In conclusion, CXCR4 contributes to later stages of plaque progression by perturbing neutrophil function.
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影响因子：
20.1
作者：
't Hoen, PAC;Van der Lans, CAC;Twisk, J
通讯作者：
Twisk, J
通过缺氧对趋化因子受体CXCR4的调节。
DOI：
10.1084/jem.20030267
发表时间：
2003-11-03
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
37.8
作者：
Bentzon, Jacob F.;Sondergaard, Claus S.;Falk, Erling
通讯作者：
Falk, Erling
影响因子：
6.7
作者：
Braunersreuther, Vincent;Mach, Francois;Steffens, Sabine
通讯作者：
Steffens, Sabine
影响因子：
15.9
作者：
Eash, Kyle J.;Greenbaum, Adam M.;Link, Daniel C.
通讯作者：
Link, Daniel C.