High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma

John T. Berg, Zhenxing Fu, Ellen C. Breen, Hung-Cuong Tran, Odile Mathieu-Costello, and John B. West Department of Medicine, University of California San Diego, La Jolla, California 92093-0623 Received 23 September 1996; accepted in final form 7 March 1997. Berg, John T., Zhenxing Fu, Ellen C. Breen, Hung-Cuong Tran, Odile Mathieu-Costello, and John B. West. High lung inflation increases mRNA levels of ECM components and growth factors in lung parenchyma. J. Appl. Physiol. 83(1): 120-128, 1997. Remodeling of pulmonary capillaries occurs after chronic increases in capillary pressure (e.g., mitral stenosis). Also, remodeling of pulmonary arteries begins within 4 h of increased wall stress and is endothelium dependent. We have previously shown that high lung inflation increases wall stress in pulmonary capillaries. This study was designed to determine whether high lung inflation induces remodeling of the extracellular matrix (ECM) in lung parenchyma. Open-chest rabbits were ventilated for 4 h with 9-cmH 2 O positive end-expiratory pressure (PEEP) on one lung and 1-cmH 2 O PEEP on the other (High-PEEP group), or with 2-cmH 2 O PEEP on both lungs (Low-PEEP group). An additional untreated control group was also included. We found increased levels of mRNA in both lungs of High-PEEP rabbits (compared with both the Low-PEEP and untreated groups) for 1 (III) and 2 (IV) procollagen, fibronectin, basic fibroblast growth factor, and transforming growth factor- 1 . In contrast, 2 (I) procollagen and vascular endothelial growth factor mRNA levels were not changed. We conclude that high lung inflation for 4 h increases mRNA levels of ECM components and growth factors in lung parenchyma. extracellular matrix; messenger ribonucleic acid; stress failure; wall tension; vascular remodeling; strength of capillaries 0161-7567/97 $5.00 Copyright © 1997 the American Physiological Society