| Autor: |
Robert, Fabien, Certain, Marie-Caroline, Baron, Audrey, Thuillet, Raphaël, Duhaut, Léa, Ottaviani, Mina, Chelgham, Mustapha Kamel, Normand, Corinne, Berrebeh, Nihel, Ricard, Nicolas, Furlan, Valerie, Desroches-Castan, Agnès, Gonzales, Emmanuel, Jacquemin, Emmanuel, Sitbon, Olivier, Humbert, Marc, Bailly, Sabine, Coilly, Audrey, Guignabert, Christophe, Tu, Ly |
| Předmět: |
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| Zdroj: |
American Journal of Respiratory & Critical Care Medicine; 9/1/2024, Vol. 210 Issue 5, p648-661, 14p |
| Abstrakt: |
Rationale: Hepatopulmonary syndrome (HPS) is a severe complication of liver diseases characterized by abnormal dilation of pulmonary vessels, resulting in impaired oxygenation. Recent research highlights the pivotal role of liver-produced BMP-9 (bone morphogenetic protein-9) in maintaining pulmonary vascular integrity. Objectives: This study aimed to investigate the involvement of BMP-9 in human and experimental HPS. Methods: Circulating BMP-9 levels were measured in 63 healthy control subjects and 203 patients with cirrhosis with or without HPS. Two animal models of portal hypertension were employed: common bile duct ligation with cirrhosis and long-term partial portal vein ligation without cirrhosis. Additionally, the therapeutic effect of low-dose BMP activator FK506 was investigated, and the pulmonary vascular phenotype of BMP-9–knockout rats was analyzed. Measurements and Main Results: Patients with HPS related to compensated cirrhosis exhibited lower levels of circulating BMP-9 compared with patients without HPS. Patients with severe cirrhosis exhibited consistently low levels of BMP-9. HPS characteristics were observed in animal models, including intrapulmonary vascular dilations and an increase in the alveolar-arterial gradient. HPS development in both rat models correlated with reduced intrahepatic BMP-9 expression, decreased circulating BMP-9 level and activity, and impaired pulmonary BMP-9 endothelial pathway. Daily treatment with FK506 for 2 weeks restored the BMP pathway in the lungs, alleviating intrapulmonary vascular dilations and improving gas exchange impairment. Furthermore, BMP-9–knockout rats displayed a pulmonary HPS phenotype, supporting its role in disease progression. Conclusions: The study findings suggest that portal hypertension–induced loss of BMP-9 signaling contributes to HPS development. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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