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Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth
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Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Vascular Medicine".

Deadline for manuscript submissions: closed (31 March 2021) | Viewed by 23677

Special Issue Editors

Dr. George N. Kouvelos

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Guest Editor
Department of Vascular Surgery, University of Thessaly, 41334 Larissa, Greece
Interests: endovascular; aortic aneurysm; thoracoabdominal aneurysm; complex aneurysm carotid stenosis; angioplasty; stenting
Special Issues, Collections and Topics in MDPI journals
Dr. Konstantinos Spanos

E-Mail Website
Guest Editor
Department of Vascular Surgery, University of Thessaly, 41334 Larissa, Greece
Interests: aortic aneurysm; thoracoabdominal aneurysm; aortic dissection; atheromatosis; complex aneurysm; aortic biology; endovascular treatment; peripheral aneurysm
Special Issues, Collections and Topics in MDPI journals
Dr. Athanasios Katsargyris

E-Mail
Guest Editor
Department of Vascular and Endovascular Surgery, Paracelsus Medical University, Nuremberg, Germany
Interests: abdominal aortic aneurysm; endovascular repair; complex aortic disease; carotid disease; atherosclerosis; stents

Special Issue Information

Dear Colleagues,

Abdominal aortic aneurysm (AAA) is an important cause of morbidity and mortality worldwide. AAA management is directed mainly by aneurysm size during subsequent periodic surveillance imaging. A threshold diameter of 55 mm has been widely used to treat AAAs, either endovascularly or by open repair. There has been continuous research during the past decade to investigate medical treatments that may limit AAA growth. First, there were several preclinical studies, followed by a small wave of clinical trials in humans.

This Special Issue aims to provide an update of research being undertaken to identify methods of reducing the rate of AAA growth, including perceptions of some of the challenges experienced in this research and current investigations on identifying treatment targets to limit AAA growth. Accordingly, this Special Issue will try to provide a forum for high-quality original research and review articles to showcase the most recent advances in limiting abdominal aortic aneurysm growth.

Prof. George N. Kouvelos
Dr. Konstantinos Spanos
Prof. Athanasios Katsargyris
Guest Editors

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • abdominal aortic aneurysm
  • aneurysm growth
  • limit aneurysm growth
  • medical therapy

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Published Papers (7 papers)

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Research

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16 pages, 3980 KiB  
Article
Animal Model Dependent Response to Pentagalloyl Glucose in Murine Abdominal Aortic Injury
by Jennifer L. Anderson, Elizabeth E. Niedert, Sourav S. Patnaik, Renxiang Tang, Riley L. Holloway, Vangelina Osteguin, Ender A. Finol and Craig J. Goergen
J. Clin. Med. 2021, 10(2), 219; https://doi.org/10.3390/jcm10020219 - 9 Jan 2021
Cited by 6 | Viewed by 3225
Abstract
Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two [...] Read more.
Abdominal aortic aneurysms (AAAs) are a local dilation of the aorta and are associated with significant mortality due to rupture and treatment complications. There is a need for less invasive treatments to prevent aneurysm growth and rupture. In this study, we used two experimental murine models to evaluate the potential of pentagalloyl glucose (PGG), which is a polyphenolic tannin that binds to and crosslinks elastin and collagen, to preserve aortic compliance. Animals underwent surgical aortic injury and received 0.3% PGG or saline treatment on the adventitial surface of the infrarenal aorta. Seventeen mice underwent topical elastase injury, and 14 mice underwent topical calcium chloride injury. We collected high-frequency ultrasound images before surgery and at 3–4 timepoints after. There was no difference in the in vivo effective maximum diameter due to PGG treatment for either model. However, the CaCl2 model had significantly higher Green–Lagrange circumferential cyclic strain in PGG-treated animals (p < 0.05). While ex vivo pressure-inflation testing showed no difference between groups in either model, histology revealed reduced calcium deposits in the PGG treatment group with the CaCl2 model. These findings highlight the continued need for improved understanding of PGG’s effects on the extracellular matrix and suggest that PGG may reduce arterial calcium accumulation. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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32 pages, 2120 KiB  
Article
Dysregulation of microRNA Modulatory Network in Abdominal Aortic Aneurysm
by Daniel P. Zalewski, Karol P. Ruszel, Andrzej Stępniewski, Dariusz Gałkowski, Jacek Bogucki, Łukasz Komsta, Przemysław Kołodziej, Paulina Chmiel, Tomasz Zubilewicz, Marcin Feldo, Janusz Kocki and Anna Bogucka-Kocka
J. Clin. Med. 2020, 9(6), 1974; https://doi.org/10.3390/jcm9061974 - 24 Jun 2020
Cited by 13 | Viewed by 3324
Abstract
Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene [...] Read more.
Abdominal artery aneurysm (AAA) refers to abdominal aortic dilatation of 3 cm or greater. AAA is frequently underdiagnosed due to often asymptomatic character of the disease, leading to elevated mortality due to aneurysm rupture. MiRNA constitute a pool of small RNAs controlling gene expression and is involved in many pathologic conditions in human. Targeted panel detecting altered expression of miRNA and genes involved in AAA would improve early diagnosis of this disease. In the presented study, we selected and analyzed miRNA and gene expression signatures in AAA patients. Next, generation sequencing was applied to obtain miRNA and gene-wide expression profiles from peripheral blood mononuclear cells in individuals with AAA and healthy controls. Differential expression analysis was performed using DESeq2 and uninformative variable elimination by partial least squares (UVE-PLS) methods. A total of 31 miRNAs and 51 genes were selected as the most promising biomarkers of AAA. Receiver operating characteristics (ROC) analysis showed good diagnostic ability of proposed biomarkers. Genes regulated by selected miRNAs were determined in silico and associated with functional terms closely related to cardiovascular and neurological diseases. Proposed biomarkers may be used for new diagnostic and therapeutic approaches in management of AAA. The findings will also contribute to the pool of knowledge about miRNA-dependent regulatory mechanisms involved in pathology of that disease. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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19 pages, 2766 KiB  
Article
The TAGA Study: A Study of Factors Determining Aortic Diameter in Families at High Risk of Abdominal Aortic Aneurysm Reveal Two New Candidate Genes
by Olga Peypoch, Ferran Paüls-Vergés, Miquel Vázquez-Santiago, Jaime Dilme, Jose Romero, Jordi Giner, Vicente Plaza, Jose Roman Escudero, Jose Manuel Soria, Mercedes Camacho and Maria Sabater-Lleal
J. Clin. Med. 2020, 9(4), 1242; https://doi.org/10.3390/jcm9041242 - 24 Apr 2020
Cited by 2 | Viewed by 3475
Abstract
A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A [...] Read more.
A variety of disorders are known to be related with aortic geometry, among them abdominal aortic aneurysm (AAA). This work aims to present the main determinants of abdominal aortic diameter in a new cohort of families at high risk of AAA. The Triple-A Genomic Analysis (TAGA) study comprises 407 individuals related in 12 families. Each family was collected through a proband with AAA. We calculated heritability and genetic correlations between abdominal aortic diameter and clinical parameters. A genome-wide linkage scan was performed based on 4.6 million variants. A predictive model was calculated with conditional forest. Heritability of the abdominal aortic diameter was 34%. Old age, male sex, higher height, weight, creatinine levels in serum, and better lung capacity were the best predictors of aortic diameter. Linkage analyses suggested the implication of Epidermal Growth Factor Receptor (EGFR) and Betacellulin (BTC) genes with aortic diameter. This is the first study to evaluate genetic components of variation of the aortic diameter in a population of AAA high-risk individuals. These results reveal EGFR, a gene that had been previously implicated in AAA, as a determinant of aortic diameter variation in healthy genetically enriched individuals, and might indicate that a common genetic background could determine the diameter of the aorta and future risk of AAA. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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8 pages, 812 KiB  
Article
Calprotectin and Receptor for Advanced Glycation End Products as a Potential Biomarker in Abdominal Aortic Aneurysm
by Willy Hauzer, Wojciech Witkiewicz and Jan Gnus
J. Clin. Med. 2020, 9(4), 927; https://doi.org/10.3390/jcm9040927 - 28 Mar 2020
Cited by 7 | Viewed by 2274
Abstract
Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the [...] Read more.
Experiments conducted in recent years on animals and research works worldwide show a linkage between calprotectin and occurrence and development of the abdominal aortic aneurysm (AAA). Additionally, a correlation between the level of the receptor for advanced glycation end products (RAGE) and the diameter of the abdominal aorta was found. The purpose of this study was to investigate whether calprotectin and the RAGE plasma level may be a biomarker of human AAA occurrence. We determined two groups of research participants: a group of 32 patients aged 53–88 undergoing primary endovascular aneurysm repair and a control group of 43 volunteers aged 59–82 without the AAA. All the patients from the study group had their blood samples drawn in order to determine the level of calprotectin and RAGE in plasma. The second follow-up examination was carried out after three months. The concentration of calprotectin and RAGE in plasma was determined with the use of the immunoenzymatic method (ELISA). The study showed that patients with the AAA had significantly higher mean calprotectin and RAGE plasma levels (p = 0.0001 and p = 0.0002, respectively) as compared to the control group. After the AAA repair operations, the level of concentration of the calprotectin decreased significantly (p = 0.0002). So far, no studies on the connection between the increase of the calprotectin and RAGE in the patient’s plasma with the AAA have been published. Calprotectin may be a promising biomarker related to the occurrence of AAA. Larger studies are needed to fully elucidate and confirm the role of calprotectin in the development and progression of the aneurysm. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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13 pages, 2172 KiB  
Article
Life Expectancy after Surgery for Ascending Aortic Aneurysm
by Daniel Hernandez-Vaquero, Jacobo Silva, Alain Escalera, Rubén Álvarez-Cabo, Carlos Morales, Rocío Díaz, Pablo Avanzas, Cesar Moris and Isaac Pascual
J. Clin. Med. 2020, 9(3), 615; https://doi.org/10.3390/jcm9030615 - 25 Feb 2020
Cited by 14 | Viewed by 4963
Abstract
Introduction: The life expectancy of patients who undergo ascending aortic replacement is unknown. The life expectancy of a population depends on a collection of environmental and socio-economic factors of the territory where they reside. Our aim was to compare the life expectancy [...] Read more.
Introduction: The life expectancy of patients who undergo ascending aortic replacement is unknown. The life expectancy of a population depends on a collection of environmental and socio-economic factors of the territory where they reside. Our aim was to compare the life expectancy of patients undergoing surgery for ascending aortic aneurysm with that of the general population matching by age, sex, and territory. In addition, we aimed to know the late complications, causes of death and risk factors. Methods: All patients who underwent elective replacement of an ascending aortic aneurysm at our institution between 2000 and 2019 were included. The long-term survival of the sample was compared with that of the general population using data of the National Institute of Statistics. Results: For patients who survived the postoperative period, observed cumulative survival at three, five and eight years was 94.07% (95% CI 91.87–95.70%), 89.96% (95% CI 86.92–92.33%) and 82.72% (95% CI 77.68–86.71%). Cumulative survival of the general population at three, five and eight years was 93.22%, 88.30%, and 80.27%. Cancer and cardiac failure were the main causes of death. Conclusions: Long-term survival of patients undergoing elective surgery for ascending aortic aneurysm who survive the postoperative period completely recover their life expectancy. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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Review

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11 pages, 500 KiB  
Review
Imaging Predictive Factors of Abdominal Aortic Aneurysm Growth
by Petroula Nana, Konstantinos Spanos, Konstantinos Dakis, Alexandros Brodis and George Kouvelos
J. Clin. Med. 2021, 10(9), 1917; https://doi.org/10.3390/jcm10091917 - 28 Apr 2021
Cited by 5 | Viewed by 2326
Abstract
Background: Variable imaging methods may add important information about abdominal aortic aneurysm (AAA) progression. The aim of this study is to assess available literature data regarding the predictive imaging factors of AAA growth. Methods: This systematic review was conducted using the PRISMA guidelines. [...] Read more.
Background: Variable imaging methods may add important information about abdominal aortic aneurysm (AAA) progression. The aim of this study is to assess available literature data regarding the predictive imaging factors of AAA growth. Methods: This systematic review was conducted using the PRISMA guidelines. A review of the literature was conducted, using PubMed, EMBASE and CENTRAL databases. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Primary outcomes were defined as AAA growth rate and factors associated to sac expansion. Results: The analysis included 23 studies. All patients (2244; mean age; 69.8 years, males; 85%) underwent imaging with different modalities; the initial evaluation was followed by one or more studies to assess aortic expansion. AAA initial diameter was reported in 13 studies (range 19.9–50.9 mm). Mean follow-up was 34.5 months. AAA diameter at the end was ranging between 20.3 and 55 mm. The initial diameter and intraluminal thrombus were characterized as prognostic factors associated to aneurysm expansion. A negative association between atherosclerosis and AAA expansion was documented. Conclusions: Aneurysm diameter is the most studied factor to be associated with expansion and the main indication for intervention. Appropriate diagnostic modalities may account for different anatomical characteristics and identify aneurysms with rapid growth and higher rupture risk. Future perspectives, including computed mathematical models that will assess wall stress and elasticity and further flow characteristics, may offer valuable alternatives in AAA growth prediction. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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19 pages, 720 KiB  
Review
Circulating Biomarkers for the Prediction of Abdominal Aortic Aneurysm Growth
by Petroula Nana, Konstantinos Dakis, Alexandros Brodis, Konstantinos Spanos and George Kouvelos
J. Clin. Med. 2021, 10(8), 1718; https://doi.org/10.3390/jcm10081718 - 16 Apr 2021
Cited by 23 | Viewed by 3354
Abstract
Background: Abdominal aortic aneurysm represents a distinct group of vascular lesions, in terms of surveillance and treatment. Screening and follow-up of patients via duplex ultrasound has been well established and proposed by current guidelines. However, serum circulating biomarkers could earn a position in [...] Read more.
Background: Abdominal aortic aneurysm represents a distinct group of vascular lesions, in terms of surveillance and treatment. Screening and follow-up of patients via duplex ultrasound has been well established and proposed by current guidelines. However, serum circulating biomarkers could earn a position in individualized patient surveillance, especially in cases of aggressive AAA growth rates. A systematic review was conducted to assess the correlation of AAA expansion rates with serum circulating biomarkers. Methods: A data search of English medical literature was conducted, using PubMed, EMBASE, and CENTRAL, until 7 March 2021, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement (PRISMA) guidelines. Studies reporting on humans, on abdominal aortic aneurysm growth rates and on serum circulating biomarkers were included. No statistical analysis was conducted. Results: A total of 25 studies with 4753 patients were included. Studies were divided in two broad categories: Those reporting on clinically applicable (8 studies) and those reporting on experimental (17 studies) biomarkers. Twenty-three out of 25 studies used duplex ultrasound (DUS) for following patients. Amongst clinically applicable biomarkers, D-dimers, LDL-C, HDL-C, TC, ApoB, and HbA1c were found to bear the most significant association with AAA growth rates. In terms of the experimental biomarkers, PIIINP, osteopontin, tPA, osteopontin, haptoglobin polymorphisms, insulin-like growth factor I, thioredoxin, neutrophil extracellular traps (NETs), and genetic factors, as polymorphisms and microRNAs were positively correlated with increased AAA expansion rates. Conclusion: In the presence of future robust data, specific serum biomarkers could potentially form the basis of an individualized surveillance strategy of patients presenting with increased AAA growth rates. Full article
(This article belongs to the Special Issue Challenges and Opportunities in Limiting Abdominal Aortic Aneurysm Growth)
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