Pulmonary Arterial Hypertension and Consecutive Right Heart Failure Lead to Liver Fibrosis

Frontiers in Cardiovascular Medicine

article

Florian Hamberger¹  Ekaterina Legchenko²  Philippe Chouvarine²  Young Seon Mederacke¹  Richard Taubert¹  Martin Meier³  Danny Jonigk⁴  Georg Hansmann²  Ingmar Mederacke¹ 

[1] Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School;Department of Pediatric Cardiology and Critical Care, Hannover Medical School;Laboratory Animal Science, Small Animal Imaging Center, Hannover Medical School;Institute of Pathology, Hannover Medical School;Member of the German Center for Lung Research ,(DZL), Biomedical Research in Endstage and Obstructive Lung Disease Hannover

关键词: congestive hepatopathy;    pulmonary arterial hypertension;    liver fibrosis;    hepatic stellate cells;    hypoxia;   

DOI  :  10.3389/fcvm.2022.862330

学科分类：地球科学(综合)

来源: Frontiers

【 摘 要 】

Hepatic congestion occurs in patients with right heart failure and can ultimately lead to liver fibrosis or cardiac cirrhosis. Elevated pulmonary arterial pressure is found in patients with hepatic congestion. However, whether pulmonary arterial hypertension (PAH) can be a cause of liver fibrosis is unknown. The aim of this study was to investigate whether rats in the SuHx model with severe PAH develop liver fibrosis and to explore the mechanisms of congestive hepatic fibrosis both in rats and humans. To achieve this, PAH was induced in six to eight-week old male Sprague Dawley rats by a single subcutaneous injection of the VEGFR 2 inhibitor SU5416 and subsequent hypoxia for 3 weeks, followed by a 6-week period in room air. SuHx-exposed rats developed severe PAH, right ventricular hypertrophy (RVH), and consecutive right ventricular failure. Cardiac magnetic resonance imaging (MRI) and histological analysis revealed that PAH rats developed both hepatic congestion and liver fibrosis. Gene set enrichment analysis (GSEA) of whole liver RNA sequencing data identified a hepatic stellate cell specific gene signature in PAH rats. Consistently, tissue microarray from liver of patients with histological evidence of hepatic congestion and underlying heart disease revealed similar fibrogenic gene expression patterns and signaling pathways. In conclusion, severe PAH with concomitant right heart failure leads to hepatic congestion and liver fibrosis in the SU5416/hypoxia rat PAH model. Patients with PAH should therefore be screened for unrecognized liver fibrosis.

【 授权许可】

CC BY