scholarly journals A Dual Role of Heme Oxygenase-1 in Angiotensin II-Induced Abdominal Aortic Aneurysm in the Normolipidemic Mice

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 163
Author(s):  
Aleksandra Kopacz ◽  
Damian Klóska ◽  
Ewa Werner ◽  
Karolina Hajduk ◽  
Anna Grochot-Przęczek ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Heme Oxygenase ◽  
Dual Role ◽  
Heme Oxygenase 1 ◽  
Blood Pressure Elevation ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal aortic aneurysm (AAA) bears a high risk of rupture and sudden death of the patient. The pathogenic mechanisms of AAA remain elusive, and surgical intervention represents the only treatment option. Heme oxygenase-1 (HO-1), a heme degrading enzyme, is induced in AAA, both in mice and humans. HO-1 was reported to mitigate AAA development in an angiotensin II (AngII)-induced model of AAA in hyperlipidemic ApoE-/- mice. Since the role of hyperlipidaemia in the pathogenesis of AAA remains controversial, we aimed to evaluate the significance of HO-1 in the development and progression of AAA in normolipidemic animals. The experiments were performed in HO-1-deficient mice and their wild-type counterparts. We demonstrated in non-hypercholesterolemic mice that the high-dose of AngII leads to the efficient formation of AAA, which is attenuated by HO-1 deficiency. Yet, if formed, they are significantly more prone to rupture upon HO-1 shortage. Differential susceptibility to AAA formation does not rely on enhanced inflammatory response or oxidative stress. AAA-resistant mice are characterized by an increase in regulators of aortic remodeling and angiotensin receptor-2 expression, significant medial thickening, and delayed blood pressure elevation in response to AngII. To conclude, we unveil a dual role of HO-1 deficiency in AAA in normolipidemic mice, where it protects against AAA development, but exacerbates the state of formed AAA.

scholarly journals Induction of Heme Oxygenase‐1 Is Linked to the Severity of Disease in Human Abdominal Aortic Aneurysm

2021 ◽  
Author(s):  
Anja Hofmann ◽  
Margarete Müglich ◽  
Steffen Wolk ◽  
Yazan Khorzom ◽  
Pamela Sabarstinski ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Heme Oxygenase ◽  
Case Fatality ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Severity Of Disease ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Background Rupture of abdominal aortic aneurysm (rAAA) is associated with high case fatality rates, and risk of rupture increases with the AAA diameter. Heme oxygenase‐1 (gene HMOX1 , protein HO‐1) is a stress‐induced protein and induction has protective effects in the vessel wall. HMOX1 −/− mice are more susceptible to angiotensin II‐induced AAA formation, but the regulation in human nonruptured and ruptured AAA is only poorly understood. Our hypothesis proposed that HO‐1 is reduced in AAA and lowering is inversely associated with the AAA diameter. Methods and Results AAA walls from patients undergoing elective open repair (eAAA) or surgery because of rupture (rAAA) were analyzed for aortic HMOX1 /HO‐1 expression by quantitative real‐time polymerase chain reaction and Western blot. Aortas from patients with aortic occlusive disease served as controls. HMOX1 /HO‐1 expression was 1.1‐ to 7.6‐fold upregulated in eAAA and rAAA. HO‐1 expression was 3‐fold higher in eAAA specimen with a diameter >84.4 mm, whereas HO‐1 was not different in rAAA. Other variables that are known for associations with AAA and HO‐1 induction were tested. In eAAA, HO‐1 expression was negatively correlated with aortic collagen content and oxidative stress parameters H 2 O 2 release, oxidized proteins, and thiobarbituric acid reactive substances. Serum HO‐1 concentrations were analyzed in patients with eAAA, and maximum values were found in an aortic diameter of 55 to 70 mm with no further increase >70 mm, compared with <55 mm. Conclusions Aortic HO‐1 expression was increased in eAAA and rAAA. HO‐1 increased with the severity of disease but was additionally connected to less oxidative stress and vasoprotective mechanisms.

scholarly journals Possible Dual Role of Decorin in Abdominal Aortic Aneurysm

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120689 ◽  
Author(s):  
Koshiro Ueda ◽  
Koichi Yoshimura ◽  
Osamu Yamashita ◽  
Takasuke Harada ◽  
Noriyasu Morikage ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Dual Role ◽  
Abdominal Aortic

scholarly journals Inhibition of Peptidyl Arginine Deiminase 4-Dependent Neutrophil Extracellular Trap Formation Reduces Angiotensin II-Induced Abdominal Aortic Aneurysm Rupture in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Ming Wei ◽  
Xia Wang ◽  
Yanting Song ◽  
Di Zhu ◽  
Dan Qi ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Angiotensin Ii ◽  
Aortic Aneurysm ◽  
Tissue Injury ◽  
Arginine Deiminase ◽  
Tunel Staining ◽  
Ang Ii ◽  
Elastin Degradation ◽  
Abdominal Aortic

Objective: Neutrophil infiltration plays an important role in the initiation and development of abdominal aortic aneurysm (AAA). Recent studies suggested that neutrophils could release neutrophil extracellular traps (NETs), leading to tissue injury in cardiovascular diseases. However, the role of NETs in AAA is elusive. This study aimed to investigate the role and underlying mechanism of NETs in AAA development.Methods and Results: An angiotensin II (Ang II) infusion-induced AAA model was established to investigate the role of NETs during AAA development. Immunofluorescence staining showed that citrullinated histone 3 (citH3), myeloperoxidase (MPO), and neutrophil elastase (NE) (NET marker) expressions were significantly increased in Ang II-infused ApoE−/− mice. The circulating double-stranded DNA (dsDNA) level was also elevated, indicating the increased NET formation during AAA. PAD4 inhibitor YW3-56 inhibited Ang II-induced NET formation. Disruption of NET formation by YW3-56 markedly reduced Ang II-induced AAA rupture, as revealed by decreased aortic diameter, vascular smooth muscle cell (VSMC) apoptosis, and elastin degradation. Apoptosis of VSMC was evaluated by TUNEL staining and Annexin V-FITC/PI staining through flow cytometry. Western blot and inhibition experiments revealed that NETs induced VSMC apoptosis via p38/JNK pathway, indicating that PAD4-dependent NET formation played an important role in AAA.Conclusions: This study suggests that PAD4-dependent NET formation is critical for AAA rupture, which provides a novel potential therapeutic strategy for AAA disease.

GT Microsatellite Repeats in the Heme Oxygenase-1 Gene Promoter Associated with Abdominal Aortic Aneurysm in Croatian Patients

2013 ◽  
Vol 51 (5-6) ◽  
pp. 482-492 ◽  
Author(s):  
Andrea Crkvenac Gregorek ◽  
Kristina Crkvenac Gornik ◽  
Darija Stupin Polancec ◽  
Sanja Dabelic
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Heme Oxygenase ◽  
Gene Promoter ◽  
Heme Oxygenase 1 ◽  
Microsatellite Repeats ◽  
Abdominal Aortic

scholarly journals Heme Oxygenase-1 Expression Affects Murine Abdominal Aortic Aneurysm Progression

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0149288 ◽  
Author(s):  
Junya Azuma ◽  
Ronald J. Wong ◽  
Takeshi Morisawa ◽  
Mark Hsu ◽  
Lars Maegdefessel ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1 ◽  
Abdominal Aortic

Heme oxygenase-1 gene promoter polymorphism is associated with abdominal aortic aneurysm

2002 ◽  
Vol 106 (2) ◽  
pp. 131-136 ◽  
Author(s):  
Martin Schillinger ◽  
Markus Exner ◽  
Wolfgang Mlekusch ◽  
Hans Domanovits ◽  
Kurt Huber ◽  
...  
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Heme Oxygenase ◽  
Gene Promoter ◽  
Promoter Polymorphism ◽  
Heme Oxygenase 1 ◽  
Abdominal Aortic ◽  
Gene Promoter Polymorphism

Current evidence and prospects for medical treatment of abdominal aortic aneurysms

VASA ◽  
2005 ◽  
Vol 34 (4) ◽  
pp. 217-223 ◽  
Author(s):  
Diehm ◽  
Schmidli ◽  
Dai-Do ◽  
Baumgartner
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Medical Treatment ◽  
Endovascular Treatment ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Current Evidence ◽  
Significant Morbidity ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abdominal aortic aneurysm (AAA) is a potentially fatal condition with risk of rupture increasing as maximum AAA diameter increases. It is agreed upon that open surgical or endovascular treatment is indicated if maximum AAA diameter exceeds 5 to 5.5cm. Continuing aneurysmal degeneration of aortoiliac arteries accounts for significant morbidity, especially in patients undergoing endovascular AAA repair. Purpose of this review is to give an overview of the current evidence of medical treatment of AAA and describe prospects of potential pharmacological approaches towards prevention of aneurysmal degeneration of small AAAs and to highlight possible adjunctive medical treatment approaches after open surgical or endovascular AAA therapy.

Gender differences in abdominal aortic aneurysm therapy – a systematic review

VASA ◽  
2018 ◽  
Vol 47 (4) ◽  
pp. 267-272 ◽  
Author(s):  
Konstanze Stoberock ◽  
Tilo Kölbel ◽  
Gülsen Atlihan ◽  
Eike Sebastian Debus ◽  
Nikolaos Tsilimparis ◽  
...  
Keyword(s):  
Gender Differences ◽  
Abdominal Aortic Aneurysm ◽  
Survival Rate ◽  
Aortic Aneurysm ◽  
Endovascular Treatment ◽  
Aortic Aneurysms ◽  
Lower Survival Rate ◽  
Lower Survival ◽  
Abdominal Aortic ◽  
Risk Of Rupture

Abstract. This article analyses if and to what extent gender differences exist in abdominal aortic aneurysm (AAA) therapy. For this purpose Medline (PubMed) was searched from January 1999 to January 2018. Keywords were: “abdominal aortic aneurysm”, “gender”, “prevalence”, “EVAR”, and “open surgery of abdominal aortic aneurysm”. Regardless of open or endovascular treatment of abdominal aortic aneurysms, women have a higher rate of complications and longer hospitalizations compared to men. The majority of studies showed that women have a lower survival rate for surgical and endovascular treatment of abdominal aneurysms after both elective and emergency interventions. Women receive less surgical/interventional and protective medical treatment. Women seem to have a higher risk of rupture, a lower survival rate in AAA, and a higher rate of complications, regardless of endovascular or open treatment. The gender differences may be due to a higher age of women at diagnosis and therapy associated with higher comorbidity, but also because of genetic, hormonal, anatomical, biological, and socio-cultural differences. Strategies for treatment in female patients must be further defined to optimize outcome.

scholarly journals Comparison of open versus endovascular surgical treatment of abdominal aortic aneurysm

2020 ◽  
Vol 6 (3) ◽  
pp. 477-480
Author(s):  
Sabine Kischkel ◽  
Carsten M. Bünger
Keyword(s):  
Abdominal Aortic Aneurysm ◽  
Aortic Aneurysm ◽  
Treatment Options ◽  
Prosthetic Graft ◽  
Healthcare Research ◽  
Vascular Medicine ◽  
Related Complication ◽  
Abdominal Aortic ◽  
Open Aortic Repair ◽  
Risk Of Rupture

AbstractAbdominal aortic aneurysm (AAA) is a common condition of increasing prevalence, particularly among older men. An AAA is defined as a permanent dilation of the abdominal aorta, with a diameter greater than 30 mm or a diameter greater than 50% of the aortic diameter at the level of the diaphragm. As the size of the aneurysm increases, so does the risk of rupture. Therefore, prophylactic repair with insertion of a prosthetic graft is offered. Since 1951 traditional open aneurysm repair (OAR) was reported and minimally invasive endovascular repair (EVAR) was first reported in 1986. Data from four randomized controlled trials (EVAR-1, DREAM, OVER, ACE) for abdominal aortic aneurysm, which enrolled almost 3000 patients, in a period from 1999 to 2008, were summarized. In addition, registry databases on the treatment of AAA of average 4000 patients per year, based from 2015 to 2018 of the German Institute for Vascular Medicine Healthcare Research of the German Society for Vascular Surgery and Vascular Medicine, were compared. The EVAR procedure for AAA showed a lower risk of perioperative mortality but was associated with a higher cardiovascular and aneurysm-related complication rate. In particular, patients aged 80 years or older benefited from EVAR since the 30-day mortality of patients receiving OAR was higher. In mid-term and long-term follow-up there were no differences in survival after endovascular and open aortic repair. Overall, it depends on the respective underlying disease and anatomy which of the two approaches is to be preferred. In conclusion, both treatment options can be considered as equal and can be offered to patients.

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