Reutersberg Benedikt, Metschl Susanne, Salvermoser Michael, Eckstein Hans-Henning, Knappich Christoph, Maegdefessel Lars, Jaroslav Pelisek, Busch Albert
Department for Vascular and Endovascular Surgery, Munich Vascular Biobank, Munich Aortic Center (MAC), University Hospital Klinikum rechts der Isar, Technical University of Munich, Germany.
Department for Vascular Surgery, University Hospital Zurich, Switzerland.
Vasa. 2023 Mar;52(2):124-132. doi: 10.1024/0301-1526/a001049. Epub 2022 Dec 15.
Abdominal aortic aneurysm (AAA) rupture is still associated with a mortality rate of 80-90%. Imaging techniques or molecular fingerprinting for patient-specific risk stratification to identify pending rupture are still lacking. The chemokine (C-X-C motif) receptor (CXCR4) activation by CXCL12 ligand has been identified as a marker of inflammation and atherosclerosis, associated with AAA. Both are highly expressed in the aortic aneurysm wall. However, it is still unclear whether different expression levels of CXCR4 and CXCL12 can distinguish ruptured AAAs (rAAA) from intact AAAs (iAAA). Abdominal aortic tissue samples (rAAA: n=29; iAAA: n=54) were excised during open aortic repair. Corresponding serum samples from these patients (n=9 from rAAAs; n=47 from iAAA) were drawn pre-surgery. Healthy aortic tissue samples (n=8) obtained from adult kidney donors during transplantation and serum samples from healthy adult volunteers were used as controls (n=5 each). CXCR4 was mainly expressed in the media of the aneurysmatic tissue. Focal positive staining was also observed in areas of inflammatory infiltrates within the adventitia. In tissue lysates, no significant differences between iAAA, rAAA, and healthy controls were observed upon ELISA analysis. In serum samples, the level of CXCR4 was significantly increased in rAAA by 4-fold compared to healthy controls (=0.011) and 3.0-fold for rAAA compared to iAAA (<0.001). Furthermore a significant positive correlation between aortic diameter and serum CXCR4 concentration was found for both, iAAA and rAAA (=0.042). Univariate logistic regression analysis showed that increased CXCR4 serum concentrations were associated with AAA rupture (OR: 4.28, 95% CI: 1.95-12.1, =0.001). CXCR4 concentration was significantly increased in serum of rAAA patients and showed a significant correlation with an increased aortic diameter. The level of CXCR4 in serum was associated with a more than 4-fold risk increase for rAAA and thus could possibly serve as a biomarker in the future. However, further validation in larger studies is required.
腹主动脉瘤（AAA）破裂的死亡率仍高达80-90%。目前仍缺乏用于患者特异性风险分层以识别即将破裂的成像技术或分子指纹识别方法。趋化因子（C-X-C基序）受体（CXCR4）被CXCL12配体激活已被确定为与AAA相关的炎症和动脉粥样硬化的标志物。二者在主动脉瘤壁中均高表达。然而，CXCR4和CXCL12的不同表达水平是否能区分破裂性腹主动脉瘤（rAAA）和未破裂性腹主动脉瘤（iAAA）仍不清楚。在开放性主动脉修复术中切除腹主动脉组织样本（rAAA：n=29；iAAA：n=54）。术前采集这些患者的相应血清样本（rAAA患者9例；iAAA患者47例）。将移植过程中从成年肾供体获得的健康主动脉组织样本（n=8）以及健康成年志愿者的血清样本用作对照（各n=5）。CXCR4主要表达于动脉瘤组织的中膜。在外膜的炎症浸润区域也观察到局灶性阳性染色。在组织裂解物中，ELISA分析未观察到iAAA、rAAA和健康对照之间存在显著差异。在血清样本中，rAAA中CXCR4水平相比健康对照显著升高4倍（P=0.011），相比iAAA升高3.0倍（P<0.001）。此外，iAAA和rAAA的主动脉直径与血清CXCR4浓度之间均存在显著正相关（P=0.042）。单因素逻辑回归分析显示，血清CXCR4浓度升高与AAA破裂相关（比值比：4.28，95%置信区间：1.95-12.1，P=0.001）。rAAA患者血清中CXCR4浓度显著升高，且与主动脉直径增加显著相关。血清中CXCR4水平与rAAA风险增加4倍以上相关，因此未来可能可作为一种生物标志物。然而，需要在更大规模的研究中进行进一步验证。
