RT Journal Article SR Electronic T1 Association between age-dependent changes in the pulmonary renin angiotensin system and severity of lung injury JF European Respiratory Journal JO Eur Respir J FD European Respiratory Society SP PA3032 DO 10.1183/13993003.congress-2015.PA3032 VO 46 IS suppl 59 A1 Laura Schouten A1 Hendrik Helmerhorst A1 Gerry Wagenaar A1 Rene Lutter A1 Joris Roelofs A1 Tom Haltenhof A1 Job Van Woensel A1 Anton Van Kaam A1 Albert Bos A1 Marcus Schultz A1 Thomas Walter A1 Roelie Wösten-van-Asperen YR 2015 UL http://erj.ersjournals.com/content/46/suppl_59/PA3032.abstract AB Background: A growing body of evidence indicates that age plays a critical role in the development and outcome of ARDS. However, the molecular mechanisms linking aging with ARDS have not been elucidated. An age-dependent imbalance in the pulmonary renin-angiotensin system (RAS) might form an explanation.Objectives: We investigated whether there are age-related changes in the pulmonary RAS in an animal model of acute lung injury (ALI). We hypothesized that during ALI, aging is associated with a shift from the lung protective pathway [Angiotensin converting enzyme (ACE) 2] to the lung injurious pathway [ACE], thereby increasing the inflammatory mediator response and lung injury.Methods: Lung injury was induced in rats of four different age groups (infants, juveniles, adults, and elderly) by intratracheal administration of LPS and mechanical ventilation.Results: With increasing age, ACE activity in bronchoalveolar lavage fluid increased (from 0.05 RFU/min in infants to 0.16 RFU/min in elderly; p for trend = 0.02). In contrast, membrane-bound ACE activity in lung-homogenate declined, indicating shedding. No changes in ACE2 activity were found, thereby shifting the balance in the alveolar compartment towards the injurious pathway. This age-dependent imbalance was associated with increased inflammatory mediator response and lung injury (wet-to-dry ratio and histology).Conclusions: Our data shows that increasing age is associated with higher ACE activity in the alveolar compartment which correlates with aggravated inflammation and lung injury. These changes should be taken into account in terms of dosing and effectiveness of RAS modulating agents for treatment of ARDS.