Down-regulation of lysyl oxydase-like in aging and venous insufficiency
G. Pascual1, C. Mendieta1, R.P. Mecham3, P. Sommer4, J.M. Bellón2 and J. Buján1
1Department of Medical Specialities, Networking Research Center on Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain, 2Department of Surgery, Faculty of Medicine, University of Alcala, Alcalá de Henares, Madrid, Spain, 3Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO, USA and 4Institut de Biologie et Chimie des Proteines, Centre National de la Recherche Scientifique, Lyon, France.
Offprint requests to: Prof. Julia Buján, Department of Medical Specialities, Faculty of Medicine, University of Alcalá, Ctra. Madrid-Barcelona Km 33,600, 28871 Alcalá de Henares, Madrid, Spain. e-mail: mjulia.bujan@uah.es
Summary. Background: Elastin expression is higher in tissues where elastic fibres are essential for the correct maintenance of function such as blood vessels. Elastin expression usually diminishes with age, however, it may be re-expressed in response to injury or repair processes. Some authors attribute the characteristic loss of elasticity of the varicose vein to a drop in the population of smooth muscle cells in the media layer. A reduction in elastin has been observed in chronic venous insufficiency, but little is known about some of the factors involved in elastin synthesis such as lysyl oxidases. The aim of this study was to examine the in vivo expression of the elastin precursor, tropoelastin (TE), and lysyl oxidase-like 1 (LOXL1), a cross-linking enzyme responsible for elastin polymer deposition. The effects of age on these expression patterns were also evaluated. Methods: Saphenous vein segments were obtained during surgery from organ donors (controls, n=20) and subjects with venous insufficiency (varicose veins, n=20). Both these groups were subdivided according to subject age into <50 years (n=10) and ≥50 years (n=10). Control and varicose vein tissue specimens were immunolabelled using anti-tropoelastin and anti-LOXL1 antibodies and also subjected to Western blot analysis. Results: Our results indicate that the levels of these markers of elastin synthesis (LOXL/tropoelastin) in the vein wall diminish in a significant way (p<0.05) with the age factor. Excluding the age factor, LOXL1 was significantly decreased in the varicose condition (p<0.05). In the younger pathological population they showed an inverse relationship (LOXL decreased, tropoelastin increased). Conclusions: The already established reduction in elastin in the varicose condition may be related, at least in part, to the decreased LOXL1 levels observed here. These events could reduce spontaneous reticulation of elastin and the partial loss of tissue elasticity in this group of patients. Histol Histopathol 23, 179-186 (2008)
Key words: Varicose vein, Chronic venous insufficiency, LOXL1, Tropoelastin, Elastin synthesis
DOI: 10.14670/HH-23.179