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Biomedicines
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Potential Medical Treatments of Abdominal Aortic Aneurysms
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Potential Medical Treatments of Abdominal Aortic Aneurysms

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 8414

Special Issue Editors

Dr. Jane Stubbe

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Guest Editor
Cardiovascular and Renal Research Unit, Institute for Molecular Medicine, University of Southern Denmark, 5000 Odense, Denmark
Interests: abdominal aortic aneurysms; hypertension; atherosclerosis; vascular remodeling
Prof. Dr. Jes Sanddal Lindholt

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Guest Editor
1. The Research Unit of Cardiac, Thoracic and Vascular Surgery, Odense University Hospital, 5000 Odense, Denmark
2. Department of Clinical Research, University of Southern Denmark, 5000 Odense, Denmark
Interests: abdominal aortic aneurysm; medical treatment; therapy; expansion; inhibition; pathophysiology; translational research

Special Issue Information

Dear Colleagues,

An abdominal aortic aneurysm (AAA) refers to localized enlargement of the aorta. Globally, AAA rupture is a major cause of death, being responsible for the death of 1% of men above the age of 65 years. Today, patients with known AAAs are monitored, and will be offered surgical repair when the AAA diameter is above 5–6 cm. Thus, there is an urgent unmet clinical need for medical therapies for small AAAs, to prevent progressive dilatation, acute or elective surgical repair, rupture, and deaths.

This Special Issue aims to provide novel insights into the pathogenesis of AAA, with therapeutic possibilities, identifying potential new biomarkers, enabling clinicians to follow AAA expansion and the potential need for surgical repair, possibly by using a translational approach. There is a need to identify novel therapeutic targets of AAA progression, potentially involving vaccines, gene therapies, cell-based therapies, targeted specific antibodies, or recombinant therapeutic proteins. Furthermore, there is a need to develop new delivery systems, directed to reach and work at the site of the aneurysm, using nanobiotechnology. Finally, we welcome reviews highlighting novel medical treatments of AAA, as well as repurposed prescription therapeutic studies for drug redisposing to treat AAA.

Dr. Jane Stubbe
Prof. Dr. Jes Sanddal Lindholt
Guest Editors

Manuscript Submission Information

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Keywords

  • abdominal aortic aneurysm
  • biomarkers
  • therapeutic targeting AAA
  • translational research
  • animal models
  • pathophysiological mechanisms

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Published Papers (4 papers)

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Research

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19 pages, 28051 KiB  
Article
Nicotine Administration Augments Abdominal Aortic Aneurysm Progression in Rats
by Hana Hadzikadunic, Tea Bøvling Sjælland, Jes S. Lindholt, Lasse Bach Steffensen, Hans Christian Beck, Egle Kavaliunaite, Lars Melholt Rasmussen and Jane Stubbe
Biomedicines 2023, 11(5), 1417; https://doi.org/10.3390/biomedicines11051417 - 10 May 2023
Cited by 2 | Viewed by 2616
Abstract
Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAAs). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesize that low-dose nicotine impairs the [...] Read more.
Inflammation and elastin degradation are key hallmarks in the pathogenesis of abdominal aortic aneurysms (AAAs). It has been acknowledged that activation of alpha7 nicotinic acetylcholine receptors (α7nAChRs) attenuates inflammation, termed the cholinergic anti-inflammatory pathway (CAP). Thus, we hypothesize that low-dose nicotine impairs the progression of elastase-induced AAAs in rats by exerting anti-inflammatory and anti-oxidative stress properties. Male Sprague–Dawley rats underwent surgical AAA induction with intraluminal elastase infusion. We compared vehicle rats with rats treated with nicotine (1.25 mg/kg/day), and aneurysm progression was monitored by weekly ultrasound images for 28 days. Nicotine treatment significantly promoted AAA progression (p = 0.031). Additionally, gelatin zymography demonstrated that nicotine significantly reduced pro-matrix metalloproteinase (pro-MMP) 2 (p = 0.029) and MMP9 (p = 0.030) activity in aneurysmal tissue. No significant difference was found in the elastin content or the score of elastin degradation between the groups. Neither infiltrating neutrophils nor macrophages, nor aneurysmal messenger RNA (mRNA) levels of pro- or anti-inflammatory cytokines, differed between the vehicle and nicotine groups. Finally, no difference in mRNA levels of markers for anti-oxidative stress or the vascular smooth muscle cells’ contractile phenotype was observed. However, proteomics analyses of non-aneurysmal abdominal aortas revealed that nicotine decreased myristoylated alanine-rich C-kinase substrate and proteins, in ontology terms, inflammatory response and reactive oxygen species, and in contradiction to augmented AAAs. In conclusion, nicotine at a dose of 1.25 mg/kg/day augments AAA expansion in this elastase AAA model. These results do not support the use of low-dose nicotine administration for the prevention of AAA progression. Full article
(This article belongs to the Special Issue Potential Medical Treatments of Abdominal Aortic Aneurysms)
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9 pages, 631 KiB  
Article
Association of Oral Anticoagulation Prescription with Clinical Events in Patients with an Asymptomatic Unrepaired Abdominal Aortic Aneurysm
by Jonathan Golledge, Jason Jenkins, Michael Bourke, Bernard Bourke and Tejas P. Singh
Biomedicines 2022, 10(9), 2112; https://doi.org/10.3390/biomedicines10092112 - 29 Aug 2022
Cited by 4 | Viewed by 1586
Abstract
Background: Most abdominal aortic aneurysms (AAA) have large volumes of intraluminal thrombus which has been implicated in promoting the risk of major adverse events. The aim of this study was to examine the association of therapeutic anticoagulation with AAA-related events and major adverse [...] Read more.
Background: Most abdominal aortic aneurysms (AAA) have large volumes of intraluminal thrombus which has been implicated in promoting the risk of major adverse events. The aim of this study was to examine the association of therapeutic anticoagulation with AAA-related events and major adverse cardiovascular events (MACE) in patients with an unrepaired AAA. Methods: Patients with an asymptomatic unrepaired AAA were recruited from four sites in Australia. The primary outcome was the combined incidence of AAA repair or AAA rupture-related mortality (AAA-related events). The main secondary outcome was MACE (the combined incidence of myocardial infarction, stroke, or cardiovascular death). The associations of anticoagulation with these outcomes were assessed using Cox proportional hazard analyses (reporting hazard ratio, HR, and 95% confidence intervals, CI) to adjust for other risk factors. Results: A total of 1161 patients were followed for a mean (standard deviation) of 4.9 (4.0) years. Of them, 536 (46.2%) patients had a least one AAA-related event and 319 (27.5%) at least one MACE. In the sample, 98 (8.4%) patients were receiving long-term therapeutic anticoagulation using warfarin (84), apixaban (7), rivaroxaban (6), or dabigatran (1). Prescription of an anticoagulant was associated with a reduced risk of an AAA-related event (adjusted HR 0.61; 95% CI 0.42, 0.90, p = 0.013), but not MACE (HR 1.16; 95% CI 0.78, 1.72, p = 0.476). Conclusions: These findings suggest that AAA-related events but not MACE may be reduced in patients prescribed an anticoagulant medication. Due to the inherent biases of observational studies, a randomized controlled trial is needed to assess whether anticoagulation reduces the risk of AAA-related events. Full article
(This article belongs to the Special Issue Potential Medical Treatments of Abdominal Aortic Aneurysms)
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Review

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11 pages, 286 KiB  
Review
Towards Precritical Medical Therapy of the Abdominal Aortic Aneurysm
by Lucia Musumeci, Wolf Eilenberg, Joël Pincemail, Koichi Yoshimura and Natzi Sakalihasan
Biomedicines 2022, 10(12), 3066; https://doi.org/10.3390/biomedicines10123066 - 29 Nov 2022
Cited by 2 | Viewed by 1859
Abstract
Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, [...] Read more.
Pharmacotherapy for abdominal aortic aneurysm (AAA) can be useful for prevention, especially in people at higher risk, for slowing down AAA progression, as well as for post-surgery adjuvant treatment. Our review focuses on novel pharmacotherapy approaches targeted towards slowing down progression of AAA, known also as secondary prevention therapy. Guidelines for AAA are not specific to slow down the expansion rate of an abdominal aortic aneurysm, and therefore no medical therapy is recommended. New ideas are urgently needed to develop a novel medical therapy. We are hopeful that in the future, pharmacologic treatment will play a key role in the prevention and treatment of AAA. Full article
(This article belongs to the Special Issue Potential Medical Treatments of Abdominal Aortic Aneurysms)
30 pages, 9426 KiB  
Review
Potential of Disease-Modifying Anti-Rheumatic Drugs to Limit Abdominal Aortic Aneurysm Growth
by Shivshankar Thanigaimani, Muhammad Ibrahim and Jonathan Golledge
Biomedicines 2022, 10(10), 2409; https://doi.org/10.3390/biomedicines10102409 - 26 Sep 2022
Cited by 5 | Viewed by 1749
Abstract
Inflammation is strongly implicated in the pathogenesis of abdominal aortic aneurysms (AAA). This review examined the potential role of biologic disease-modifying anti-rheumatic drugs (bDMARDs) as repurposed drugs for treating AAA. Published evidence from clinical and preclinical studies was examined. Findings from animal models [...] Read more.
Inflammation is strongly implicated in the pathogenesis of abdominal aortic aneurysms (AAA). This review examined the potential role of biologic disease-modifying anti-rheumatic drugs (bDMARDs) as repurposed drugs for treating AAA. Published evidence from clinical and preclinical studies was examined. Findings from animal models suggested that a deficiency or inhibition of tumour necrosis factor-α (TNF-α) (standard mean difference (SMD): −8.37, 95% confidence interval (CI): −9.92, −6.82), interleukin (IL)-6 (SMD: −1.44, 95% CI: −2.85, −0.04) and IL-17 (SMD: −3.36, 95% CI: −4.21, −2.50) led to a significantly smaller AAA diameter compared to controls. Human AAA tissue samples had significantly increased TNF-α (SMD: 1.68, 95% CI: 0.87, 2.49), IL-1β (SMD: 1.93, 95% CI: 1.08, 2.79), IL-6 (SMD: 2.56, 95% CI: 1.79, 3.33) and IL-17 (SMD: 6.28, 95% CI: 3.57, 8.99) levels compared to non-AAA controls. In human serum, TNF-α (SMD: 1.11, 95% CI: 0.25, 1.97) and IL-6 (SMD: 1.42, 95% CI: 0.91, 1.92) levels were significantly elevated compared to non-AAA controls. These findings implicate TNF-α, IL-17 and IL-6 in AAA pathogenesis. Randomised controlled trials testing the value of bDMARDs in limiting AAA growth may be warranted. Full article
(This article belongs to the Special Issue Potential Medical Treatments of Abdominal Aortic Aneurysms)
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