CXCR4: A Potential Marker for Inflammatory Activity in Abdominal Aortic Aneurysm Wall.
OBJECTIVE
The aim of the study was to evaluate the potential role of chemokine receptor CXCR4 and its ligand CXCL12 in the pathogenesis of abdominal aortic aneurysm (AAA).


METHODS
AAA tissue specimens were obtained from the anterior or lateral aneurysm sac of patients (n = 32, 26 males, 6 females; 66.8 ± 11.2 years, diameter 64.4 ± 17.0 mm), who underwent elective open surgical repair. Twelve non-aneurysmal aortic specimens from transplant donors served as controls. Expression analysis of CXCR4 and CXCL12 at mRNA and protein level was determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR) and western blot. Immunohistochemical staining of corresponding histological sections for CD3 (T-cells), CD20 (B-cells), and CD68 (macrophages) was performed to determine the cellular localization of CXCR4 and CXCL12. Data were analyzed with SPSS 20.0 using Mann-Whitney U test and Spearman's rank correlation coefficient.


RESULTS
Gene expression of CXCR4 and CXCL12 was 9.6 and 4.6 fold higher in AAA than in non-aneurysmal aorta (p = .0004 and p < .0001, respectively). Likewise, the protein level of CXCR4 was increased 3.2 fold in AAA wall compared with non-aneurysmal aortic tissue (p < .0001), although CXCL12 could not be detected. Immunohistochemical analysis revealed that CXCR4 was expressed in B and T lymphocytes and macrophages, and CXCL12 was observed only in plasma cells.


CONCLUSIONS
This study confirmed the over expression of CXCR4 in human AAA tissue. CXCR4 was detected both at the mRNA and the protein level and by immunohistochemistry, especially in inflammatory cells. In contrast, CXCL12 expression was observed only at the mRNA level, with the exception of plasma cells. The exact role of CXCR4/CXCL12 in AAA has to be further elucidated.
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.
F
F
Tanios
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany. Electronic address: jaroslav.pelisek@tum.de.
J
J
Pelisek
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.
B
B
Lutz
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.
B
B
Reutersberg
Department of Surgery, Munich Transplant Centre, Klinikum rechts der Isar, Munich, Germany.
E
E
Matevossian
Institute of Pathology, Klinikum rechts der Isar, Munich, Germany.
K
K
Schwamborn
Department of Mathematical Modeling of Biological Systems, Technische Universität München, Munich, Germany.
V
V
Hösel
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.
H-H
HH
Eckstein
Department of Vascular and Endovascular Surgery, Klinikum rechts der Isar, Munich, Germany.
C
C
Reeps
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001012:Aorta, Abdominal / Q000737:chemistry* / Q000000981:diagnostic imaging / Q000601:surgery; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000235:genetics / Q000378:metabolism* / Q000601:surgery; D001027:Aortography / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D015153:Blotting, Western; D016022:Case-Control Studies; D054377:Chemokine CXCL12 / Q000032:analysis / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018836:Inflammation Mediators / Q000032:analysis*; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D019718:Receptors, CXCR4 / Q000032:analysis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014057:Tomography, X-Ray Computed; D015854:Up-Regulation
D015415:Biomarkers; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D018836:Inflammation Mediators; D012333:RNA, Messenger; D019718:Receptors, CXCR4
Abdominal aortic aneurysm; CXCL12; CXCR4; Gene expression; Inflammatory processes