Abdominal aortic aneurysm (AAA) rupture is an important cause of death in adults. Currently, the only treatment for AAA is open or endovascular surgical repair. In most parts of the developed world, AAAs can be identified at an early stage as a result of incidental imaging and screening programmes. Randomized clinical trials have demonstrated that early elective surgical repair of these small AAAs is not beneficial, and an unmet clinical need exists to develop medical therapies for small AAAs that limit or prevent the progressive expansion and rupture of the aneurysm. A large amount of research is currently being performed to increase the understanding of AAA pathogenesis and ultimately lead to the development of medical therapies, such as drug-based and cell-based strategies for this disease. This Review summarizes the latest research findings and current theories on AAA pathogenesis, including discussion of the pros and cons of current rodent models of AAA, and highlights potential medical therapies for AAA, summarizing previous, ongoing and potential clinical trials of medical interventions for small AAAs. This expanding volume of research on AAA is expected to result in a range of novel medical therapies for AAA within the next decade.

Abdominal aortic aneurysm: update on pathogenesis and medical treatments.

An abdominal aortic aneurysm (AAA) is a localized dilatation of the infrarenal aorta. AAA is a multifactorial disease, and genetic and environmental factors play a part; smoking, male sex and a positive family history are the most important risk factors, and AAA is most common in men >65 years of age. AAA results from changes in the aortic wall structure, including thinning of the media and adventitia due to the loss of vascular smooth muscle cells and degradation of the extracellular matrix. If the mechanical stress of the blood pressure acting on the wall exceeds the wall strength, the AAA ruptures, causing life-threatening intra-abdominal haemorrhage — the mortality for patients with ruptured AAA is 65–85%. Although AAAs of any size can rupture, the risk of rupture increases with diameter. Intact AAAs are typically asymptomatic, and in settings where screening programmes with ultrasonography are not implemented, most cases are diagnosed incidentally. Modern functional imaging techniques (PET, CT and MRI) may help to assess rupture risk. Elective repair of AAA with open surgery or endovascular aortic repair (EVAR) should be considered to prevent AAA rupture, although the morbidity and mortality associated with both techniques remain non-negligible. An abdominal aortic aneurysm (AAA) is an enlargement of the abdominal aorta. As the AAA grows, the aortic wall becomes progressively thin, and the risk of rupture increases; AAA rupture causes severe intra-abdominal haemorrhage and has a very high mortality.

Abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) is an important health problem. Elective surgical treatment is recommended on the basis of an individual's risk of rupture, which is predicted by AAA diameter. However, the natural history of AAA differs between patients and a reliable and individual predictor of AAA progression (growth and expansion rates) has not been established. Several circulating biomarkers are candidates for an AAA diagnostic tool. However, they have yet to meet the triad of biomarker criteria: biological plausibility, correlation with AAA progression, and prediction of treatment effect on disease outcome. Circulating levels of markers of extracellular matrix degeneration, such as elastin peptides, aminoterminal propeptide of type III procollagen, elastase-alpha1-antitrypsin complexes, matrix metalloproteinase 9, cystatin C, plasmin-antiplasmin complexes and tissue plasminogen activator, have been correlated with AAA progression and have biological plausibility. Although studies of these markers have shown promising results, they have not yet led to a clinically applicable biomarker. In future studies, adjustment for initial AAA size, smoking history and the measurement error for determination of AAA size, among other variables, should be taken into account. A large, prospective, standardized, follow-up study will be needed to investigate multiple circulating biomarkers for their potential role in the prediction of AAA progression, followed by a study to investigate the effect of treatment on the circulating levels of biomarkers.

Biomarkers of AAA progression. Part 1: extracellular matrix degeneration

Defining progression of abdominal aortic aneurysm (AAA) is complicated by several factors, including measurement error, duration of follow-up, and the imaging modality used to assess AAA expansion. Investigations of biomarkers of AAA progression should be standardized so that valid comparisons can be made. Previous research has shown some promising advances towards identifying a reliable and individual predictor of AAA progression. In this second part of our Review on biomarkers of AAA progression, we examine direct and indirect markers of inflammation including various cytokines, C-reactive protein, activators of tissue plasminogen activator and urokinase plasminogen activator, and osteopontin.

Biomarkers of abdominal aortic aneurysm progression. Part 2: inflammation.

Over the past decade, chemical labeling with isobaric tandem mass tags, such as isobaric tags for relative and absolute quantification reagents (iTRAQ) and tandem mass tag (TMT) reagents, has been employed in a wide range of different clinically orientated serum and plasma proteomics studies. In this review the scope of these works is presented with attention to the areas of research, methods employed and performance limitations. These applications have covered a wide range of diseases, disorders and infections, and have implemented a variety of different preparative and mass spectrometric approaches. In contrast to earlier works, which struggled to quantify more than a few hundred proteins, increasingly these studies have provided deeper insight into the plasma proteome extending the numbers of quantified proteins to over a thousand.

Analysis of the plasma proteome using iTRAQ and TMT-based Isobaric labeling.

Abdominal aortic aneurysm (AAA) evolution is unpredictable, and there is no therapy except surgery for patients with an aortic size> 5 cm (large AAA). We aimed to identify new potential biomarkers that could facilitate prognosis and treatment of patients with AAA. A differential quantitative proteomic analysis of plasma proteins was performed in AAA patients at different stages of evolution [small AAA (aortic size=3–5cm) vs large AAA] using iTRAQ labelling, high-throughput nano-LC-MS/MS and a novel multi-layered statistical model. Among the proteins identified, ApoA-I was decreased in patients with large AAA compared to those with small AAA. These results were validated by ELISA on plasma samples from small (n=90) and large AAA (n=26) patients (150± 3 vs 133± 5 mg/dl, respectively, p

ApoA-I/HDL-C levels are inversely associated with abdominal aortic aneurysm progression

Search for Serum Biomarkers Associated with Abdominal Aortic Aneurysm Growth – A Pilot Study

Assessment of biomarkers and predictive model for short-term prospective abdominal aortic aneurysm growth-A pilot study.

Resumen Objetivo El diagnostico y seguimiento de los pacientes con aneurisma de aorta abdominal (AAA) se realizan mediante medicion seriada del diametro aortico maximo con ultrasonografia o tomografia computerizada, pero la expansion aortica es mayoritariamente discontinua, e impredecible en un paciente concreto. Un modelo predictivo fiable de crecimiento y/o rotura aorticos podria ayudar a individualizar el manejo. Nuestro objetivo ha sido definir un modelo predictivo de crecimiento aneurismatico a corto plazo a partir de variables clinicas, serologicas y anatomicas. Metodos Se reclutaron 148 pacientes con AAA aterosclerotico infrarrenal asintomatico consecutivos. Se recogieron: datos clinicos (edad, sexo, factores de riesgo cardiovascular, comorbilidad, medicacion), diametro basal de los AAA, crecimiento aortico prospectivo a un ano, y concentraciones basales circulantes de MMP-2, MMP-9, cistatina C, alfa1-antitripsina, mieloperoxidasa, MCP-1, homocisteina, dimero D, PAP y proteina C reactiva. Se elaboraron modelos predictivos del crecimiento prospectivo a un ano de los AAA, crecimiento valorado como variable continua (mm/ano) y dicotomica (estabilidad, si la tasa de crecimiento era ≤ 2 mm/ano; expansion, si era > 2 mm/ano), utilizando regresion lineal y logistica, simple y multiple. Resultados Cada incremento en las concentraciones de dimero D en 1 ng/mL se asocio al aumento medio de 0,0062 mm/ano en el crecimiento prospectivo de los AAA. La insuficiencia renal cronica aumento el crecimiento medio en 2,95 mm/ano. Mayores concentraciones de PAP y la coexistencia de IRC aumentaban el riesgo de expansion aortica (OR 1,01 y 14523,62; IC 95% 1,00-1,02 y 0-7,39E + 40, respectivamente). Conclusiones Las concentraciones plasmaticas de dimero D y PAP constituyen prometedores biomarcadores predictivos de la expansion prospectiva de los AAA a corto plazo. La insuficiencia renal cronica es un importante factor clinico pronostico de expansion aortica. La clasificacion del crecimiento de los AAA de forma dicotomica, estabilidad versus expansion, puede ser util para la elaboracion de modelos de decision y su aplicacion clinica.

Estudio de biomarcadores y modelos predictivos de crecimiento en el aneurisma de aorta abdominal

Anaemia, Iron and Vitamin Deficits in Patients with Peripheral Arterial Disease

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