Screening for abdominal aortic aneurysm

Cosford, Paul; Leng, Gillian; Thomas, Jonathan

doi:10.1002/14651858.cd002945.pub2

Cited by 309 publications

(225 citation statements)

References 32 publications

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“…A bdominal aortic aneurysm (AAA) is a common vascular disorder that affects ∼5% of men and ∼1.5% of women ages 65 and older (1,2). Rupture of AAA presents a medical emergency that accounts for 15,000 deaths annually in the United States (3).…”

mentioning

confidence: 99%

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation

Zhou

Yan

Bertram

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Abdominal aortic aneurysm (AAA) is a common vascular disease associated with high mortality rate due to progressive enlargement and eventual rupture. There is currently no established therapy known to alter the rate of aneurysmal expansion. Thus, understanding the processes that initiate and sustain aneurysmal growth is pivotal for the development of medical therapies aimed at halting disease progression. Using an elastase-induced AAA mouse model that recapitulates key features of human AAA, we previously reported that a natural IgG antibody directs alternative pathway complement activation and initiates the inflammatory process that culminates in aneurysmal development. The target of this natural antibody, however, was unknown. Herein we identify a natural IgG that binds to fibrinogen deposited in elastaseperfused aortic tissues, activates the complement lectin pathway (LP), and induces AAA. Moreover, we establish that alterations in the glycosylation patterns of this antibody critically affect its ability to activate the LP in vivo. We find that LP activation precedes the alternative pathway and absence of the LP complement protein mannan-binding lectin abrogates elastase-induced AAA. In human AAA tissues the mouse anti-fibrinogen antibody recognizes epitopes that localize to the same areas that stain positively for mannan-binding lectin, which suggests that the complement LP is engaged in humans as well. Lastly, we demonstrate that circulating antibodies in a subset of AAA patients react against fibrinogen or fibrinogen-associated epitopes in human aneurysmal tissues. Our findings support the concept that an autoimmune process directed at aortic wall self-antigens may play a central role in the immunopathogenesis of AAA.A bdominal aortic aneurysm (AAA) is a common vascular disorder that affects ∼5% of men and ∼1.5% of women ages 65 and older (1, 2). Rupture of AAA presents a medical emergency that accounts for 15,000 deaths annually in the United States (3). Currently, surgical repair represents the only treatment option for large AAAs, whereas surgery in small AAAs offers no clear overall long-term survival advantage (4, 5). Thus, medical management, to inhibit or reverse the progression of small AAAs, has received increasing attention. Major challenges remain in the development of therapeutic agents that impede aneurysm expansion, as our understanding of the pathophysiology underlying this disease is incomplete.One of the defining characteristics of AAA is inflammation accompanied by a cellular infiltrate that is predominantly lymphocytic (6-8). The elastase-induced AAA mouse model recapitulates many key features of human AAA, including the inflammatory response (9). We previously established with this model that aneurysm development requires factor B and properdin of the complement alternative pathway (AP) (10, 11). We showed that mice deficient in B cells (and hence antibodies), called μMT mice, are protected against aneurysm formation. Reconstitution with natural IgG, but not IgM, from wild-type mice res...

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mentioning

confidence: 99%

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation

Zhou

Yan

Bertram

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…14 An initial screening test in men older than 65 years reduces mortality by half from AAA in the population. 3,13,15 In this patient, the aneurysm was confirmed by ultrasound examination.…”

Section: Discussionmentioning

confidence: 52%

“…Some authors have researched the viability of screening for AAA; however, abdominal palpation is not a very sensitive tool for this. 3,4,13 It is however suggested that screening of male smokers in the 65-to 75-year age group may be useful to diagnose asymptomatic abdominal aneurysms. 7,8 Because some of the risk factors were present, a screening palpation could have been done.…”

Section: Discussionmentioning

confidence: 99%

Clinical detection of abdominal aortic aneurysm in a 74-year-old man in chiropractic practice

Boer

Knaap²,

Zoete³

2010

Journal of Chiropractic Medicine

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Objective: The purpose of this article is to present a case of abdominal aortic aneurysm to illustrate its clinical detection through history and physical examination and the importance of this condition to the chiropractic clinical setting. Clinical Features: A 74-year-old retired man consulted a doctor of chiropractic for chronic low back pain. The history and physical examination confirmed chronic sacroiliac and a lumbar facet dysfunction. After 5 weeks, the patient stated he had stomach cramps. After this, a more thorough abdominal examination was done. The doctor of chiropractic detected an enlarged pulsatile mass upon abdominal palpation. Intervention and outcome: The patient was sent to the cardiologist and had successful surgery within weeks. Conclusion: An abdominal aortic aneurysm has specific symptoms and associated risk factors. If known risk factors are present, a clinical examination needs to be carried out, even though sensitivity of the clinical examination may be low. It should be a differential diagnosis in every male patient older than 50 years with low back pain. In case of suspicion, the patient should be referred for advanced imaging.

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“…The annual growth rate with a 4.0 cm of ascending TAA is 0.10 cm, while the annual growth rate with an 8.0 cm of ascending TAA is 0.19 cm (25). In AAA, ruptures appear in 25-41% of AAAs with a diameter >50 mm over 5 years (26). In TAA, large aneurysms, especially the size greater than 5 to 6 cm, expand more rapidly compared with small aneurysms (27)(28)(29)(30)(31)(32).…”

Section: Sizementioning

confidence: 98%

Molecular targets in aortic aneurysm for establishing novel management paradigms

Zhu

et al. 2017

J. Thorac. Dis.

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Aortic aneurysm (AA) is a lethal disease and presents a large challenge for surgeons in the clinic.Although surgical management remains the major choice of AA, operative mortality remains high. With advances in understanding of the mechanisms of AAs, molecular targets, such as matrix metalloproteinases (MMPs), D-dimer, and inflammation markers, including C-reactive protein, interleukins and phagocytes, are important in the pathology of development of AA. These markers may become important for improving the diagnostic quality and provide more therapeutic choices for treatment of AA. Although these new markers require long-term trials before they can be translated into the clinic, they can still be helpful in determining new directions. The main aim of this review is to discuss the current findings of molecular targets in progression of AA and discuss the potential application of these new targets for managing this disease.

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Screening for abdominal aortic aneurysm

Cited by 309 publications

References 32 publications

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation

Fibrinogen-specific antibody induces abdominal aortic aneurysm in mice through complement lectin pathway activation

Clinical detection of abdominal aortic aneurysm in a 74-year-old man in chiropractic practice

Molecular targets in aortic aneurysm for establishing novel management paradigms

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