Autor:innen:
Dr. Anja Hofmann | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Margarete Müglich | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Dr. med. Steffen Wolk | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Yazan Khorzom | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Pamela Sabarstinski | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Prof. Dr. Irakli Kopaliani | Medizinische Fakultät an der TU Dresden | Germany
Dr. Dmitry Egorov | Medizinische Fakultät an der TU Dresden | Germany
Franziska Horn | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Dr. Coy Brunssen | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Medizinische Klinik und Poliklinik III | Germany
Dr. Sindy Giebe | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Medizinische Klinik und Poliklinik III | Germany
Bianca Hamann | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Prof. Dr. med. Andreas Deussen | Medizinische Fakultät an der TU Dresden | Germany
Prof. Dr. Henning Morawietz | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Medizinische Klinik und Poliklinik III | Germany
PD Dr. David M. Poitz | Universitätsklinikum Carl Gustav Dresden der TU Dresden | Germany
Univ. Prof. Dr. med. Christian Reeps | Universitätsklinikum Carl Gustav Dresden der TU Dresden, Klinik für Viszeral-, Thorax- und Gefäßchirurgie | Germany
Objective Rupture of abdominal aortic aneurysm (rAAA) is associated with high mortality. Heme oyxeganse-1 (gene HMOX1, protein HO-1) is a stress-induced protein and reaction products exert anti-oxidative and anti-inflammatory properties. Deletion of HMOX1 increases the susceptibility to angiotensin II-induced AAA formation in preclinical mouse models. While an induction of HO-1 is protective in various cardiovascular diseases, its role in human non-ruptured and ruptured AAA is only poorly understood. Hypothesis Our research hypothesis proposed that HO-1 is reduced in AAA and lowering is inversely associated with the AAA diameter and parameters of vessel wall degeneration. Materials and Methods AAA walls from patients undergoing elective open (eAAA, n=19) or emergency repair due to rupture (rAAA, n=11) were analyzed for aortic HMOX1/HO-1 expression by qPCR and Western blot. Aortas from patients with peripheral artery disease served as controls (n=4). Histopathological AAA wall degeneration was evaluated by elastic fiber and collagen breakdown. Oxidative stress was assessed by measuring extracellular hydrogen peroxide (H2O2), malondialdehyde (MDA) concentrations and the amount of oxidized proteins. Serum HO-1 was analyzed by enzyme-linked immunosorbent assay (ELISA) and the activity of matrix metalloprotease 9 (MMP9) by gelatin zymography. Results HMOX1/HO-1 expression was similarly increased in eAAA and rAAA. HO 1 expression tended (p=0.07) to be higher in eAAA samples with a diameter > 62 mm, whereas HO-1 was slightly (p=0.13) lowered in rAAA with a diameter > 94 mm. Secondary outcome variables known for their associations with AAA and HO-1 induction were tested. In eAAA, the increased HO-1 expression was correlated with a lowering in collagen (rS= 0.65; p=0.005, n=17), oxidative stress and slightly with the activity of matrix metalloprotease-9 (MMP9) (rS=-0.41, p=0.08, n=19). Serum HO 1 was analyzed in eAAA and maximum values were found in a diameter of 55-70 mm (p=0.04 vs. < 55 mm) with no further increase > 70 mm. Conclusions Aortic HO-1 expression was increased in non-ruptured and rAAA but the induction was not associated with the AAA diameter, rejecting our proposed research hypothesis. However, the increase was closely associated with a lowering in oxidative stress and MMP9 activity, suggesting a protective effect of the HO-1 induction.