Downregulation of Aquaporin-1 in Alveolar Microvessels in Lungs Adapted to Chronic Heart Failure
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Katrine M. Mu¨ llertz • Claes Strّm • Simon Trautner • Ole Amtorp • Sّren Nielsen • Sten Christensen • Stig Haunsّ • Thomas E. N. Jonassen
- چاپ و سال / کشور: 2011
Description
The threshold pressure for lung edema formation is increased in severe chronic heart failure (CHF) due to reduced microvascular permeability. The water channel aquaporin-1 (AQP1) is present in the pulmonary microvascular endothelium, and a number of studies suggest the importance of AQP1 as a molecular determinant of pulmonary microvascular water transport. The present study examined the abundance and localization of AQP1 in lungs from rats with CHF. We used two different models of CHF: ligation of the left anterior descending coronary artery (LAD ligation) and aorta-banding (AB). Sham-operated rats served as controls. Echocardiographic verification of left ventricular dysfunction, enhanced left ventricular end-diastolic pressure, and right ventricular hypertrophy confirmed the presence of CHF. Western blotting of wholelung homogenates revealed significant downregulation of AQP1 in LAD-ligated rats (24 h: 58 ± 5% of sham; 3 weeks: 8 ± 3% of sham; 9 weeks: 16 ± 6% of sham) and after AB (30 weeks: 37 ± 5% of sham), whereas the protein levels of the specific endothelial cell marker PECAM-1 was increased 3 weeks after LAD ligation (229 ± 20% of sham), but unchanged after 9 weeks and in the AB rats compared to controls. Immunohistochemical examination 3 weeks after LAD ligation showed intact labeling of PECAM-1 but an almost complete absence of AQP1 in the pulmonary alveolar microvessels in the CHF rats. These results suggest that downregulation of AQP1 in the alveolar microvessels may act as a compensatory mechanism to protect against formation of excessive pulmonary edema in CHF.
Lung (2011) 189:157–166 DOI 10.1007/s00408-010-9276-x Received: 18 January 2010 / Accepted: 3 December 2010 / Published online: 4 January 2011
