Influence of cardiovascular risk factors on levels of matrix metalloproteinases 2 and 9 in human abdominal aortic aneurysms.

OBJECTIVE: To evaluate the influence of cardiovascular risk factors on levels of matrix metalloproteinases (MMP) 2 and 9 in human abdominal aortic aneurysms (AAA). METHODS: Aortic samples were collected from patients who underwent AAA repair (n = 89). Patients were stratified according to the maximum transverse aorta diameter: small diameter (<55 mm), moderate diameter (55-69.9 mm) and large diameter (≥70 mm). Aortic walls were studied using real-time PCR and immunohistochemistry. MMP-2, MMP-9, α-actin, CD45, and CD68 transcript levels were determined relative to ß-actin. Quantitative data were expressed as median (IQ-range). RESULTS: No differences were found in MMP-2 expression between the patient groups, which was mainly associated with vascular smooth muscle cells (VSMC); however, MMP-9 displayed the maximum level in the moderate-diameter group, associated with infiltrating macrophages. Current smoking (CS) and renal insufficiency (RI) significantly increased local levels of MMP-2 (CS 349.5 [219.5-414.1] vs. no-CS 184.4 [100.0-320.5]; p < .008; RI 286.8 [189.6-410.8] vs. no-RI 177.3 [99.3-326.9]; p = .047). Nevertheless, after stepwise linear regression analysis only CS remained as an independent variable predicting local levels of MMP-2 (p = .002). No risk factors influenced local levels of MMP-9. CONCLUSIONS: The results show that local levels of MMP-2, an important factor for AAA development, were increased in current smoking AAA patients. MMP-2 was mainly associated with VSMC. It is suggested that MMP-2 could contribute significantly to the increased AAA growth rate observed in current smoking patients. These findings support inclusion of smokers in screening for aneurysmal disease, and emphasize the need for more aggressive monitoring of aneurysmal disease outside the surgical range in patients who smoke at the time of diagnosis and in those who continue to smoke during follow-up.

Métodos de estudio de las enfermedades complejas: aneurismas de la aorta abdominal / Methods for studying complex diseases: abdominal aortic aneurysm

Las enfermedades vasculares, particularmente el aneurisma de la aorta abdominal (AAA), tienen una base multifactorial compleja, donde múltiples interacciones entre factores genéticos y ambientales contribuyen al desarrollo de la enfermedad. Sin embargo, pese a los avances en la última década, nuestros conocimientos sobre la base genética de estas patologías son aún escasos. Este artículo presenta una revisión de los métodos para el estudio de las bases genéticas de las enfermedades vasculares focalizada en el AAA desde un enfoque de enfermedad compleja, y de índole multifactorial. La identificación y el análisis de los genes causantes de esta patología nos permitirán realizar una estratificación de los individuos con diferentes riesgos de desarrollar esta patología, mejorando las opciones preventivas y terapéuticas, lo que se traducirá en una mayor calidad de vida de las personas en riesgo(AU)

The aetiology of vascular diseases, such as abdominal aortic aneurysm (AAA), is complex and multi-factorial. The complexity derives from different genetic and environmental factors contributing to the development of these diseases. Despite the fact that a great effort has been made in the last decade to understand the genetic basis of these complex diseases there is still much to be learned. The present review deals with the methods that have been used to study the genetic bases of vascular diseases. In addition, we will focus on AAA as a complex multi-factorial disease. The identification of the genes involved in the pathophysiology of AAA will allow us to stratify individuals with different risks of developing disease, as well as improving preventive and therapeutic strategies. All of this will increase the quality of life of the persons who are in risk(AU)