Downregulation of the endothelin system of lung myofibroblasts in congestive heart failure.
Congestive heart failure (CHF) causes lung remodelling with thickening of the alveolar septa and proliferation of myofibroblasts (MYF). Endothelin-1 (ET-1) is increased in CHF and may contribute to this process. CHF was induced in rats by myocardial infarction. After three weeks there was lung remodelling with thickening of alveolar septa and increases in 5'-bromodeoxyuridine uptake and vimentin expression (P < 0.05). The mitogenic and protein synthesis response of MYF to ET-1 (10 nM) were assessed by H-thymidine and H-leucine incorporation respectively. The mitogenic response in CHF (19.0 +/- 3.0%, mean +/- SEM) was less than for sham rats (35 +/- 5.4%, P < 0.05). This was associated with a lower production of ET-1 by CHF MYF (15.15 +/- 5.67 fmol/ml) compared to sham (33.66 +/- 13.22 fmol/ml; P < 0.05). Additionally, protein expression of ETA (0.36 +/- 0.038 AU) and ETB receptors (0.24 +/- 0.075 AU) were reduced in CHF compared to shams (0.65 +/- 0.086 AU and 0.81 +/- 0.21 AU respectively; P < 0.05). There is a downregulation of the ET system of lung MYF in CHF with reduced proliferation in response to ET-1. This may represent a protective adaptation to counteract lung remodelling in response to chronic exposure to high levels of ET-1.
Préfontaine
Annick
A
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
Calderone
Angelino
A
Dupuis
Jocelyn
J
D000818:Animals; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015536:Down-Regulation; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism; D006333:Heart Failure / Q000503:physiopathology*; D008168:Lung / Q000473:pathology*; D008297:Male; D009203:Myocardial Infarction / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A / Q000235:genetics; D044023:Receptor, Endothelin B / Q000235:genetics
D019332:Endothelin-1; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B