Update on Abdominal Aortic Aneurysm Research: From Clinical to Genetic Studies

An abdominal aortic aneurysm (AAA) is a dilatation of the abdominal aorta with a diameter of at least 3.0 cm. AAAs are often asymptomatic and are discovered as incidental findings in imaging studies or when the AAA ruptures leading to a medical emergency. AAAs are more common in males than females, in individuals of European ancestry, and in those over 65 years of age. Smoking is the most important environmental risk factor. In addition, a positive family history of AAA increases the person’s risk for AAA. Interestingly, diabetes has been shown to be a protective factor for AAA in many large studies. Hallmarks of AAA pathogenesis include inflammation, vascular smooth muscle cell apoptosis, extracellular matrix degradation, and oxidative stress. Autoimmunity may also play a role in AAA development and progression. In this Outlook paper, we summarize our recent studies on AAA including clinical studies related to surgical repair of AAA and genetic risk factor and large-scale gene expression studies. We conclude with a discussion on our research projects using large data sets available through electronic medical records and biobanks.

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The Obesity-associated Risk in Open and Endovascular Repair of Abdominal Aortic Aneurysm

Current Pharmaceutical Design ◽

10.2174/1381612825666190710112844 ◽

2019 ◽

Vol 25 (18) ◽

pp. 2033-2037 ◽

Cited By ~ 2

Author(s):

Djordje Radak ◽

Slobodan Tanaskovic ◽

Mihailo Neskovic

Keyword(s):

Risk Factor ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Treatment Option ◽

Morbidly Obese ◽

Complication Rates ◽

Obese Patients ◽

Invasive Treatment ◽

Abdominal Aortic ◽

The Subject

: The rising pandemic of obesity in modern society should direct attention to a more comprehensive approach to abdominal aortic aneurysm (AAA) treatment in the affected population. Although overweight patients are considered prone to increased surgical risk, studies on the subject did not confirm or specify the risks well enough. : Associated comorbidities inevitably lead to a selection bias leaning towards endovascular abdominal aortic repair (EVAR), as a less invasive treatment option, which makes it hard to single out obesity as an independent risk factor. The increased technical difficulty often results in prolonged procedure times and increased blood loss. Several smaller studies and two analyses of national registries, including 7935 patients, highlighted the advantages of EVAR over open repair (OR) of abdominal aortic aneurysm, especially in morbidly obese population (relative risk reduction up to 47%). On the other hand, two other studies with 1374 patients combined, concluded that EVAR might not have an advantage over OR in obese patients (P = 0.52). Obesity is an established risk factor for wound infection after both EVAR and OR, which is associated with longer length of stay, subsequent major operations, and a higher rate of graft failure. Percutaneous EVAR technique could present a promising solution to reducing this complication. : EVAR seems like a more feasible treatment option than OR for obese patients with AAA, due to lower overall morbidity and mortality rates, as well as reduced wound-related complication rates. However, there is a clear lack of high-quality evidence on the subject, thus future prospective trials are needed to confirm this advantage.

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Basement membrane collagen IV deficiency promotes abdominal aortic aneurysm formation

Scientific Reports ◽

10.1038/s41598-021-92303-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

L. B. Steffensen ◽

J. Stubbe ◽

J. S. Lindholt ◽

H. C. Beck ◽

M. Overgaard ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Basement Membrane ◽

Protective Factor ◽

Complex Disease ◽

Artery Bypass ◽

Protective Role ◽

Collagen Iv ◽

Mammary Arteries ◽

Abdominal Aortic

AbstractAbdominal aortic aneurysm (AAA) is a complex disease which is incompletely accounted for. Basement membrane (BM) Collagen IV (COL4A1/A2) is abundant in the artery wall, and several lines of evidence indicate a protective role of baseline COL4A1/A2 in AAA development. Using Col4a1/a2 hemizygous knockout mice (Col4a1/a2+/−, 129Svj background) we show that partial Col4a1/a2 deficiency augmented AAA formation. Although unchallenged aortas were morphometrically and biomechanically unaffected by genotype, explorative proteomic analyses of aortas revealed a clear reduction in BM components and contractile vascular smooth muscle cell (VSMC) proteins, suggesting a central effect of the BM in maintaining VSMCs in the contractile phenotype. These findings were translated to human arteries by showing that COL4A1/A2 correlated to BM proteins and VSMC markers in non-lesioned internal mammary arteries obtained from coronary artery bypass procedures. Moreover, in human AAA tissue, MYH11 (VSMC marker) was depleted in areas of reduced COL4 as assessed by immunohistochemistry. Finally, circulating COL4A1 degradation fragments correlated with AAA progression in the largest Danish AAA cohort, suggesting COL4A1/A2 proteolysis to be an important feature of AAA formation. In sum, we identify COL4A1/A2 as a critical regulator of VSMC phenotype and a protective factor in AAA formation.

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Prior Cardiac and Thoracic Aortic Surgery as a Complication Risk Factor for Abdominal Aortic Aneurysm Repair

Circulation Journal ◽

10.1253/circj.cj-11-1511 ◽

2012 ◽

Vol 76 (6) ◽

pp. 1380-1384 ◽

Cited By ~ 3

Author(s):

Kota Yamamoto ◽

Toshihiro Fukui ◽

Shigefumi Matsuyama ◽

Minoru Tabata ◽

Haruo Aramoto ◽

...

Keyword(s):

Risk Factor ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Aortic Surgery ◽

Abdominal Aortic Aneurysm Repair ◽

Thoracic Aortic Surgery ◽

Complication Risk ◽

Abdominal Aortic ◽

Aneurysm Repair ◽

Aortic Aneurysm Repair

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Multi-drug resistance – 1 [MDR – 1, P-GL, ABC] gene polymorphism is a risk factor for development of abdominal aortic aneurysm

International Journal of the Cardiovascular Academy ◽

10.1016/j.ijcac.2016.11.004 ◽

2016 ◽

Vol 2 (4) ◽

pp. 178

Keyword(s):

Drug Resistance ◽

Risk Factor ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Gene Polymorphism ◽

Multi Drug Resistance ◽

Abdominal Aortic ◽

Mdr 1

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The similarities and differences among patients with abdominal aortic aneurysms referred to a tertiary hospital and found at necropsy

Vascular ◽

10.1177/1708538114552095 ◽

2014 ◽

Vol 23 (4) ◽

pp. 411-418 ◽

Cited By ~ 5

Author(s):

Erasmo S da Silva ◽

Vitor C Gornati ◽

Ivan B Casella ◽

Ricardo Aun ◽

Andre EV Estenssoro ◽

...

Keyword(s):

Risk Factors ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Protective Factor ◽

Abdominal Aortic Aneurysms ◽

Aortic Aneurysms ◽

Maximum Diameter ◽

Transverse Diameter ◽

Abdominal Aortic ◽

Tertiary Center

Objective To analyze the characteristics of patients with abdominal aortic aneurysms referred to a tertiary center and to compare with individuals with abdominal aortic aneurysm found at necropsy. Methods We have retrospectively analyzed the medical records of 556 patients with abdominal aortic aneurysm and 102 cases abdominal aortic aneurysm found at necropsy. Results At univariated analysis, hypertension, tobacco use and maximum diameter were significant risk factors for symptomatic aneurysm, while diabetes tended to be a protective factor for rupture. By logistic regression analysis, the largest transverse diameter was the only one significantly associated with abdominal aortic aneurysm rupture ( p < .0001, odds ratio 1.7, 95% confidence interval 1.481–1.951). Intact abdominal aortic aneurysm found at necropsy showed similarities with outpatients in relation to abdominal aortic aneurysm diameter and risk factors. Conclusion Intact abdominal aortic aneurysm at necropsy and at outpatients setting showed similarities that confirmed that abdominal aortic aneurysm repair is less offered to women, and they died more frequently with intact abdominal aortic aneurysm from other causes.

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