Clin Res Cardiol (2023). https://doi.org/10.1007/s00392-023-02180-w

CD163-Hemeoxygenase-1-Axis Is Induced in Macrophages of Abdominal Aortic Aneurysm Patients

B. Hamann1, A. Hofmann2, F. Klotz1, F. Frank1, P. Sabarstinski1, D. M. Poitz3, S. Wolk1, H. Morawietz4, C. Reeps1

1Klinik und Poliklinik für Viszeral-, Thorax- und Gefäßchirurgie (VTG), Universitätsklinik Carl Gustav Carus der TU Dresden, Dresden; 2Gefäß- und Endovaskuläre Chirurgie, Viszeral-, Thorax- und Gefäßchirurgie, Dresden; 3Institut für klinische Chemie und Laboratoriumsmedizin, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden; 4Med. Klinik III, Gefäßendothel/Mikrozirkulation, Universitätsklinikum Carl Gustav Carus an der TU Dresden, Dresden;

Introduction Abdominal aortic aneurysm (AAA) is a common vascular pathology in elderly people. AAA are clinical silent until rupture, a life-threatening condition. Intramural hemorrhage is associated with an increased risk for AAA rupture. Hemolysis of erythrocytes causes the release of hemoglobin, which is a pro-oxidative compound due to its iron content. Clearance of hemoglobin is mediated by the scavenger receptor CD163 that is only expressed by cells of the monocyte-macrophage lineage. The incorporated heme induces heme oxygenase-1 (HO 1, HMOX1) and the differentiation towards a specific, atheroprotective hem-induced macrophage subtype. These MHem macrophages show high expressions of CD163, HO-1 and interleukine-10 (IL-10). However, nothing is known yet about the regulation of CD163, HO-1 and IL-10 in monocyte-derived macrophages in human AAA. Materials and Methods Aortic HMOX1 and CD163 mRNA expression was analyzed in electively treated and ruptured AAA patients. Primary monocytes were isolated from whole blood. To determine whether circulating monocytes were pre-primed, they were autologously differentiated. In a further attempt, the monocytes were differentiated under hemin stimulation to investigate the influence of hemorrhage on macrophage differentiation. Afterwards, CD163, IL-10 and HMOX1 mRNA expression were analyzed and compared between AAA and non-diseased controls. Results Aneurysmatic CD163 and HMOX1 mRNA expression was higher in ruptured AAA compared to electively treated patients. Concomitantly, monocyte-derived macrophages of AAA patients revealed a higher induction of CD163 and IL10 after autologous differentiation when compared to controls. During the course of differentiation, CD163 expression showed a 4-fold increase in AAA without reaching significance. Stimulation with hemin tended to further increase CD163 expression within the AAA group. Interestingly, HMOX1 declined over time during autologous differentiation, whereas differentiation under hemin increased HMOX1 expression in both groups to a similar extent. Conclusion Patients with AAA tend to have increased expression of MHem macrophage markers in aortic tissue and monocyte-derived macrophages. However, there is a difference between autologous and hemin-mediated differentiation. Future analysis of iron-responsible genes is may thus clarify this difference and the role MHem macrophages in the pathogenesis of AAA.

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