Lysyl oxidase like-1 dysregulation and its contribution to direct inguinal hernia G. Pascual *,† , M. Rodrı´guez *,† , R. P. Mecham ‡ , P. Sommer § , J. Buja ´n *,† and J. M. Bello ´n *,† * University of Alcala, Alcala ´ de Henares, Madrid, Spain, † Networking Research Centre on Biomaterials and Nanomedicine (CIBER-BBN), Madrid, Spain, ‡ Washington University School of Medicine, St Louis, MO, USA, § Centre National de la Recherche Scientifique, Lyon, France ABSTRACT Objective The aetiology of inguinal hernia involves changes in collagen turnover and metalloproteinase expression; yet it is not known whether the elastic fibre system could also be affected. This study was designed to compare the expression of tropoelastin (TE), lysyl oxidase-like 1 (LOXL-1) and elastase in the transversalis fascia of patients with and without inguinal hernia. Material and methods Transversalis fascia (TF) specimens were obtained from patients undergoing surgery for direct or indirect inguinal hernia (n = 20 each) and from multi-organ donors during organ procurement (controls, n = 16). The specimens were divided according to age (20–40 ⁄ 41–60 years). Tissues were immuno- histochemically labelled using anti-tropoelastin, anti-LOXL-1 and anti-elastase antibodies and subjected to Western blot analysis. Relative amounts of LOXL-1 and TE mRNA were determined by real time RT-PCR in cultured cells obtained from the TF of patients and controls. Results Significantly lower TE and LOXL-1 levels were observed in patients with direct inguinal hernia com- pared with controls or those with indirect hernia. In contrast, patients with direct inguinal hernia showed signifi- cantly higher elastase expression. In fibroblasts isolated from the TF, relative amounts of tropoelastin mRNA were lower for the hernia groups but differences were not significant. LOXL-1 mRNA levels were significantly lower in the direct hernia group compared to controls. Conclusions Our findings suggest that impaired elastic fibre function in the transversalis fascia of patients with direct inguinal hernia, reflected by diminished elastin synthesis and its enhanced enzyme degradation, contributes to the development of this type of hernia. Keywords Elastin metabolism, inguinal hernia, lysyl oxidases. Eur J Clin Invest 2009; 39 (4): 328–337 Introduction Inguinal hernia is still one of the entities that most frequently requires surgical treatment. Every year, around 20 million patients worldwide undergo surgery for this type of hernia [1]. Although its aetiology remains unclear, there seem to be many contributing factors added to an individual predisposition. The integrity of the abdominal wall is determined by the oblique orientation of the inguinal canal, by a sphincter-like structure that forms part of the deep inguinal ring and by the transver- salis fascia (TF) [2]. This last structure, which forms the poster- ior wall of the inguinal canal, is what eventually avoids the formation of a hernia, especially hernias of the direct type [3]. The biological factors proposed in the studies performed by Read [4–6] have gradually gained acceptance, ascribing a particularly relevant role to metabolic factors in the develop- ment of inguinal hernia. In a clarifying scheme, Jansen et al. [7] also placed inguinal hernias within the context of conditions generated by an abnormal composition of the extracellular matrix. Patients with inguinal hernia show some anomalies in collagen metabolism and altered ratios of collagen types [8,9], but little is known about the elastic component of the extracel- lular matrix and the factors involved in tissue remodelling that could affect elastin metabolism. The protein elastin is formed through the reticulation of tropoelastin (TE) monomers over a framework of fibrillin-rich microfibrils [10], and latent transforming growth factor-beta 328 European Journal of Clinical Investigation Vol 39 DOI: 10.1111/j.1365-2362.2009.02099.x ORIGINAL ARTICLE