{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T21:31:03Z","timestamp":1768253463661,"version":"3.49.0"},"reference-count":37,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MeDDrive program 2019 of the Medical Faculty of TU Dresden","award":["MO 1695\/5-1"],"award-info":[{"award-number":["MO 1695\/5-1"]}]},{"name":"MeDDrive program 2019 of the Medical Faculty of TU Dresden","award":["IRTG 2251"],"award-info":[{"award-number":["IRTG 2251"]}]},{"name":"MeDDrive program 2019 of the Medical Faculty of TU Dresden","award":["3-2, F03661-553-41B-1250000"],"award-info":[{"award-number":["3-2, F03661-553-41B-1250000"]}]},{"name":"Carus Promotionskolleg fellowship of the Medical Faculty of TU Dresden","award":["MO 1695\/5-1"],"award-info":[{"award-number":["MO 1695\/5-1"]}]},{"name":"Carus Promotionskolleg fellowship of the Medical Faculty of TU Dresden","award":["IRTG 2251"],"award-info":[{"award-number":["IRTG 2251"]}]},{"name":"Carus Promotionskolleg fellowship of the Medical Faculty of TU Dresden","award":["3-2, F03661-553-41B-1250000"],"award-info":[{"award-number":["3-2, F03661-553-41B-1250000"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["MO 1695\/5-1"],"award-info":[{"award-number":["MO 1695\/5-1"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["IRTG 2251"],"award-info":[{"award-number":["IRTG 2251"]}]},{"name":"Deutsche Forschungsgemeinschaft (DFG)","award":["3-2, F03661-553-41B-1250000"],"award-info":[{"award-number":["3-2, F03661-553-41B-1250000"]}]},{"name":"Excellence Initiative of the German federal state governments","award":["MO 1695\/5-1"],"award-info":[{"award-number":["MO 1695\/5-1"]}]},{"name":"Excellence Initiative of the German federal state governments","award":["IRTG 2251"],"award-info":[{"award-number":["IRTG 2251"]}]},{"name":"Excellence Initiative of the German federal state governments","award":["3-2, F03661-553-41B-1250000"],"award-info":[{"award-number":["3-2, F03661-553-41B-1250000"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/antiox11091753","type":"journal-article","created":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T20:48:25Z","timestamp":1662410905000},"page":"1753","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pharmacotherapies and Aortic Heme Oxygenase-1 Expression in Patients with Abdominal Aortic Aneurysm"],"prefix":"10.3390","volume":"11","author":[{"given":"Anja","family":"Hofmann","sequence":"first","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bianca","family":"Hamann","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Klimova","sequence":"additional","affiliation":[{"name":"National Center for Tumor Diseases, Partner Site Dresden, Institute for Medical Informatics and Biometry, Medical Faculty Carl Gustav Carus, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5750-5195","authenticated-orcid":false,"given":"Margarete","family":"M\u00fcglich","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2126-3067","authenticated-orcid":false,"given":"Steffen","family":"Wolk","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Albert","family":"Busch","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frieda","family":"Frank","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5732-8312","authenticated-orcid":false,"given":"Pamela","family":"Sabarstinski","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marvin","family":"Kapalla","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef Albin","family":"Nees","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine, Asklepios-ASB Klinik Radeberg, D-01454 Radeberg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Coy","family":"Brunssen","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7803-1972","authenticated-orcid":false,"given":"David M.","family":"Poitz","sequence":"additional","affiliation":[{"name":"Institute for Clinical Chemistry and Laboratory Medicine, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9360-9736","authenticated-orcid":false,"given":"Henning","family":"Morawietz","sequence":"additional","affiliation":[{"name":"Division of Vascular Endothelium and Microcirculation, Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Technische Universit\u00e4t Dresden, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian","family":"Reeps","sequence":"additional","affiliation":[{"name":"Division of Vascular and Endovascular Surgery, Department of Visceral, Thoracic and Vascular Surgery, University Hospital and Faculty of Medicine, Technische Universit\u00e4t Dresden, Fetscherstr. 74, D-01307 Dresden, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1097\/01.sla.0000150258.36236.e0","article-title":"Treatment with simvastatin suppresses the development of experimental abdominal aortic aneurysms in normal and hypercholesterolemic mice","volume":"241","author":"Steinmetz","year":"2005","journal-title":"Ann. Surg."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1016\/j.jvs.2012.07.003","article-title":"Intraluminal abdominal aortic aneurysm thrombus is associated with disruption of wall integrity","volume":"57","author":"Koole","year":"2013","journal-title":"J. Vasc. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1097\/HCO.0000000000000216","article-title":"Abdominal aortic aneurysm: Novel mechanisms and therapies","volume":"30","author":"Davis","year":"2015","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1161\/CIRCRESAHA.118.312439","article-title":"Pharmacologic Management of Aneurysms","volume":"124","author":"Lindeman","year":"2019","journal-title":"Circ. Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1093\/cvr\/cvp155","article-title":"Pharmacological treatment of abdominal aortic aneurysm","volume":"83","author":"Miyake","year":"2009","journal-title":"Cardiovasc. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1016\/j.jacc.2008.06.019","article-title":"Hemoxygenase-1 in cardiovascular disease","volume":"52","author":"Idriss","year":"2008","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1093\/eurheartj\/ehv114","article-title":"Haeme oxygenase signalling pathway: Implications for cardiovascular disease","volume":"36","author":"Fredenburgh","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"776","DOI":"10.1016\/j.redox.2017.04.008","article-title":"Cigarette smoke extract counteracts atheroprotective effects of high laminar flow on endothelial function","volume":"12","author":"Giebe","year":"2017","journal-title":"Redox Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0006-2952(00)00443-3","article-title":"Gene regulation of heme oxygenase-1 as a therapeutic target","volume":"60","author":"Immenschuh","year":"2000","journal-title":"Biochem. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1835","DOI":"10.1089\/ars.2010.3726","article-title":"A central role of heme oxygenase-1 in cardiovascular protection","volume":"15","author":"Wu","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"67760","DOI":"10.18632\/oncotarget.11917","article-title":"Heme oxygenase-1 deficiency exacerbates angiotensin II-induced aortic aneurysm in mice","volume":"7","author":"Ho","year":"2016","journal-title":"Oncotarget"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Azuma, J., Wong, R.J., Morisawa, T., Hsu, M., Maegdefessel, L., Zhao, H., Kalish, F., Kayama, Y., Wallenstein, M.B., and Deng, A.C. (2016). Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0149288"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e022747","DOI":"10.1161\/JAHA.121.022747","article-title":"Induction of Heme Oxygenase-1 Is Linked to the Severity of Disease in Human Abdominal Aortic Aneurysm","volume":"10","author":"Hofmann","year":"2021","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","first-page":"19","article-title":"The Abdominal Aortic Aneurysm and Intraluminal Thrombus: Current Concepts of Development and Treatment","volume":"2","author":"Jozkowicz","year":"2015","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"RESEARCH0034","DOI":"10.1186\/gb-2002-3-7-research0034","article-title":"Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes","volume":"3","author":"Vandesompele","year":"2002","journal-title":"Genome Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"20621","DOI":"10.1074\/jbc.M607954200","article-title":"Heme Oxygenase-1 Protein Localizes to the Nucleus and Activates Transcription Factors Important in Oxidative Stress","volume":"282","author":"Lin","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3021","DOI":"10.1093\/eurheartj\/ehy339","article-title":"2018 ESC\/ESH Guidelines for the management of arterial hypertension","volume":"39","author":"Williams","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.ejps.2010.05.021","article-title":"Simvastatin-dependent up-regulation of heme oxygenase-1 via mRNA stabilization in human endothelial cells","volume":"41","author":"Hinkelmann","year":"2010","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e0023621","DOI":"10.1128\/MCB.00236-21","article-title":"Distinct Regulations of HO-1 Gene Expression for Stress Response and Substrate Induction","volume":"41","author":"Zhang","year":"2021","journal-title":"Mol. Cell. Biol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0049-3848(02)00100-7","article-title":"Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm","volume":"106","author":"Schillinger","year":"2002","journal-title":"Thromb. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1743","DOI":"10.1089\/ars.2013.5674","article-title":"Signaling function of heme oxygenase proteins","volume":"20","author":"Dennery","year":"2014","journal-title":"Antioxid. Redox Signal."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1586\/erc.10.27","article-title":"Mechanisms for blood pressure lowering and metabolic effects of thiazide and thiazide-like diuretics","volume":"8","author":"Duarte","year":"2010","journal-title":"Expert Rev. Cardiovasc. Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1161\/01.HYP.32.6.1071","article-title":"Thiazide-Induced Vasodilation in Humans Is Mediated by Potassium Channel Activation","volume":"32","author":"Pickkers","year":"1998","journal-title":"Hypertension"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1471","DOI":"10.1152\/ajpheart.00962.2012","article-title":"Upregulation of heme oxygenase-1 potentiates EDH-type relaxations in the mesenteric artery of the spontaneously hypertensive rat","volume":"305","author":"Li","year":"2013","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1681\/ASN.2011121147","article-title":"Plasma and Urinary Heme Oxygenase-1 in AKI","volume":"23","author":"Zager","year":"2012","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2745","DOI":"10.1111\/j.1523-1755.2005.00745.x","article-title":"Increase in heme oxygenase-1 levels ameliorates renovascular hypertension","volume":"68","author":"Botros","year":"2005","journal-title":"Kidney Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1124\/jpet.114.212928","article-title":"Ramipril Protects the Endothelium from High Glucose\u2013Induced Dysfunction through CaMKK\u03b2\/AMPK and Heme Oxygenase-1 Activation","volume":"350","author":"Tian","year":"2014","journal-title":"J. Pharm. Exp. Ther."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1161\/01.HYP.29.3.790","article-title":"Heme oxygenase-1 is regulated by angiotensin II in rat vascular smooth muscle cells","volume":"29","author":"Ishizaka","year":"1997","journal-title":"Hypertension"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"I296","DOI":"10.1161\/CIRCULATIONAHA.105.001313","article-title":"Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress: The EPAS trial","volume":"114","author":"Morawietz","year":"2006","journal-title":"Circulation"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1161\/01.CIR.100.9.899","article-title":"Angiotensin II induces LOX-1, the human endothelial receptor for oxidized low-density lipoprotein","volume":"100","author":"Morawietz","year":"1999","journal-title":"Circulation"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1001\/jamacardio.2020.3524","article-title":"Efficacy of Telmisartan to Slow Growth of Small Abdominal Aortic Aneurysms: A Randomized Clinical Trial","volume":"5","author":"Golledge","year":"2020","journal-title":"JAMA Cardiol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1296","DOI":"10.1161\/01.CIR.0000140694.67251.9C","article-title":"Simvastatin Induces Heme Oxygenase-1","volume":"110","author":"Lee","year":"2004","journal-title":"Circulation"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/j.redox.2017.02.006","article-title":"Reciprocal regulation of eNOS, H2S and CO-synthesizing enzymes in human atheroma: Correlation with plaque stability and effects of simvastatin","volume":"12","author":"Sigala","year":"2017","journal-title":"Redox Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2028936","DOI":"10.1155\/2018\/2028936","article-title":"Simvastatin Treatment Upregulates HO-1 in Patients with Abdominal Aortic Aneurysm but Independently of Nrf2","volume":"2018","author":"Kopacz","year":"2018","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1161\/CIRCRESAHA.107.158998","article-title":"Heme oxygenase-1 deficiency accelerates formation of arterial thrombosis through oxidative damage to the endothelium, which is rescued by inhaled carbon monoxide","volume":"101","author":"True","year":"2007","journal-title":"Circ. Res."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Durante, W. (2020). Targeting Heme Oxygenase-1 in the Arterial Response to Injury and Disease. Antioxidants, 9.","DOI":"10.3390\/antiox9090829"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1161\/01.ATV.0000118279.74056.8a","article-title":"Vascular heme oxygenase-1 induction suppresses microvascular thrombus formation in vivo","volume":"24","author":"Lindenblatt","year":"2004","journal-title":"Arter. Thromb. Vasc. Biol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/9\/1753\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:15Z","timestamp":1760142195000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/9\/1753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,4]]},"references-count":37,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["antiox11091753"],"URL":"https:\/\/doi.org\/10.3390\/antiox11091753","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,4]]}}}