Respiratory Physiology & Neurobiology 207 (2015) 58–60 Contents lists available at ScienceDirect Respiratory Physiology & Neurobiology journal h om epa ge: www.elsevier.com/locate/resphysiol Short communication Increased upper airway collapsibility in a mouse model of Marfan syndrome Renata Kelly da Palma a,b , Ramon Farré a,c , Josep Maria Montserrat c,d , Darya Gorbenko Del Blanco e , Gustavo Egea e , Luís Vicente Franco de Oliveira b , Daniel Navajas a,f , Isaac Almendros a,c,∗ a Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona – IDIBAPS, Barcelona, Spain b Master’s and Doctoral Degree Programs in Rehabilitation Sciences, Nove de Julho University, Sao Paulo, Brazil c CIBER Enfermedades Respiratorias, Bunyola, Spain d Laboratori de la Son, Pneumologia, Hospital Clinic-Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain e Department de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, IDIBAPS – Universitat de Barcelona, Barcelona, Spain f Institute for Bioengineering of Catalonia, Spain a r t i c l e i n f o Article history: Accepted 16 December 2014 Available online 23 December 2014 Keywords: Marfan syndrome Obstructive sleep apnea Upper airway collapsibility a b s t r a c t Marfan syndrome (MFS) is a genetic disorder caused by mutations in the FBN1 gene that codifies for fibrilin-1. MFS affects elastic fiber formation and the resulting connective tissue shows abnormal tissue laxity and organization. Although an increased prevalence of obstructive sleep apnea among patients with MFS has been described, the potential effects of this genetic disease on the collapsible properties of the upper airway are unknown. The aim of this study was to assess the collapsible properties of the upper airway in a mouse model of MFS Fbn1( C1039G/+ ) that is representative of most of the clinical manifestations observed in human patients. The upper airway in wild-type and Marfan mice was cannulated and its critical pressure (P crit ) was measured in vivo by increasing the negative pressure through a controlled pressure source. P crit values from MFS mice were higher (less negative) compared to wild-type mice (-3.1 ± 0.9 cmH 2 O vs. -7.8 ± 2.0 cm H 2 O) suggesting that MFS increases the upper airway collapsibility, which could in turn explain the higher prevalence of OSA in MFS patients. © 2014 Elsevier B.V. All rights reserved. 1. Introduction The Marfan syndrome (MFS) is an autosomal dominant disorder of the connective tissue affecting approximately 1 in 5000 people. Cardiovascular disease (mainly progressive aortic-root dilatation and dissection) is the leading cause of death by MFS, but the disease also causes long bone overgrowth, dislocation of the ocu- lar lens, musculoskeletal and pulmonary dysfunctions (Ca˜ nadas et al., 2010). These abnormalities are caused by mutations local- ized within the FBN1 gene that encodes fibrillin-1, a component of extracellular microfibrills and therefore of elastic fibers. OSA is a prevalent disorder characterized by repetitive events of collapse and reopening of the upper airway during sleep. The higher ∗ Corresponding author at: Unitat de Biofisica i Bioenginyeria, Facultat de Medi- cina, Universitat de Barcelona, Casanova 143, 08036 Barcelona, Spain. Tel.: +34 93 402 4515; fax: +34 93 403 5278. E-mail address: isaac.almendros@ub.edu (I. Almendros). collapsibility observed in OSA is usually attributed to obesity and other alterations in structural or functional properties of the upper airway (Dempsey et al., 2010). Several studies have documented a higher prevalence of OSA among patients with MFS (Cistulli et al., 2001; Kohler et al., 2009) which has been associated to abnormal- ities in maxillary morphology and craniofacial structure (Cistulli et al., 2001). Interestingly, there is a study showing that all the MFS patients investigated exhibited increased upper airway collapsibil- ity respect to weight-matched controls. The authors suggested that this abnormally high collapsibility could be caused by MFS-induced changes in the connective tissue (Cistulli and Sullivan, 1995). Here we use a mouse model of MFS, free of other confounding factors, to investigate whether the potential structural changes in the upper airway associated to MFS could increase its collapsibility explaining in part the higher prevalence of OSA in MFS patients. Accordingly, this murine MFS model could allow interpreting the high occurrence of OSA in MFS patients, being also a use- ful model of spontaneous collapsibility for studying upper airway mechanics. http://dx.doi.org/10.1016/j.resp.2014.12.013 1569-9048/© 2014 Elsevier B.V. All rights reserved.