Pharmacotherapies and Aortic Heme Oxygenase-1 Expression in Patients with Abdominal Aortic Aneurysm

Anja Hofmann; Bianca Hamann; Anna Klimova; Margarete Müglich; Steffen Wolk; Albert Busch; Frieda Frank; Pamela Sabarstinski; Marvin Kapalla; Josef Albin Nees; Coy Brunssen; David M Poitz; Henning Morawietz; Christian Reeps

doi:10.3390/antiox11091753

Pharmacotherapies and Aortic Heme Oxygenase-1 Expression in Patients with Abdominal Aortic Aneurysm

Antioxidants (Basel). 2022 Sep 4;11(9):1753. doi: 10.3390/antiox11091753.

Affiliations

¹ Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universität Dresden, Fetscherstr. 74, D-01307 Dresden, Germany.
² National Center for Tumor Diseases, Partner Site Dresden, Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
³ Clinic for Internal Medicine, Asklepios-ASB Klinik Radeberg, D-01454 Radeberg, Germany.
⁴ Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universität Dresden, D-01307 Dresden, Germany.
⁵ Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universität Dresden, D-01307 Dresden, Germany.

Abstract

Background: Treatment of cardiovascular risk factors slows the progression of small abdominal aortic aneurysms (AAA). Heme oxygenase-1 (HO-1) is a stress- and hemin-induced enzyme providing cytoprotection against oxidative stress when overexpressed. However, nothing is known about the effects of cardiometabolic standard therapies on HO-1 expression in aortic walls in patients with end-stage AAA.

Methods: The effects of statins, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), beta-blockers, diuretics, acetylsalicylic acid (ASA), and therapeutic anticoagulation on HO-1 mRNA and protein expressions were analyzed in AAA patients using multivariate logistic regression analysis and comparison of monotherapy.

Results: Analysis of monotherapy revealed that HO-1 mRNA and protein expressions were higher in patients on diuretics and lower in patients on statin therapy. Tests on combinations of antihypertensive medications demonstrated that ACE inhibitors and diuretics, ARBs and diuretics, and beta-blockers and diuretics were associated with increase in HO-1 mRNA expression. ASA and therapeutic anticoagulation were not linked to HO-1 expression.

Conclusion: Diuretics showed the strongest association with HO-1 expression, persisting even in combination with other antihypertensive medications. Hence, changes in aortic HO-1 expression in response to different medical therapies and their effects on vessel wall degeneration should be analyzed in future studies.

Keywords: abdominal aortic aneurysm; cardiovascular risk factors; heme oxygenase-1; pharmacotherapy; vascular biology.

Grants and funding

This work was supported by grants from the MeDDrive program 2019 of the Medical Faculty of TU Dresden to A.H. M.M. received funding from the Carus Promotionskolleg fellowship of the Medical Faculty of TU Dresden. H.M. and C.B. were supported by the Deutsche Forschungsgemeinschaft (DFG) (MO 1695/5-1, IRTG 2251), and H.M. was supported by the Excellence Initiative of the German federal state governments (Institutional Strategy, measure “support the best”, grant 3-2, F03661-553-41B-1250000).