Albumin restores endothelial cell mitochondrial morphology in patients with decompensated cirrhosis

Fischer, S.E.; Postma, R.J.; Bijkerk, R.; Kerbert, A.J.C.; Zonneveld, A.J. van; Coenraad, M.J.

doi:doi:10.1111/liv.70653

Background & Aims: Endothelial cell (EC) activation is a critical driver of disease progression in cirrhosis, contributing to acute decompensation (AD) and acute- on- chronic liver failure (ACLF). Although human albumin administration improves EC function in cirrhotic patients with hypoalbuminemia, its direct effects on ECs remain unclear. This ex vivo study investigates the impact of albumin on EC morphology and mitochondrial function upon exposure to plasma from patients with decompensated cirrhosis (DC). Methods: Human umbilical vein ECs were exposed to plasma from patients with DC and hypoalbuminemia (albumin < 30 g/L, n = 20), compensated cirrhosis (CC, > 30 g/L, n = 20), or healthy controls (HC, n = 20). Albumin was added to DC and HC plasma to reach physiological (~40 g/L) or supraphysiological levels. Mitochondrial function was assessed by measuring oxygen con sumption rate (OCR) and reactive oxygen species (ROS) production. The effects of albumin on EC activation were...Show moreBackground & Aims: Endothelial cell (EC) activation is a critical driver of disease progression in cirrhosis, contributing to acute decompensation (AD) and acute- on- chronic liver failure (ACLF). Although human albumin administration improves EC function in cirrhotic patients with hypoalbuminemia, its direct effects on ECs remain unclear. This ex vivo study investigates the impact of albumin on EC morphology and mitochondrial function upon exposure to plasma from patients with decompensated cirrhosis (DC). Methods: Human umbilical vein ECs were exposed to plasma from patients with DC and hypoalbuminemia (albumin < 30 g/L, n = 20), compensated cirrhosis (CC, > 30 g/L, n = 20), or healthy controls (HC, n = 20). Albumin was added to DC and HC plasma to reach physiological (~40 g/L) or supraphysiological levels. Mitochondrial function was assessed by measuring oxygen con sumption rate (OCR) and reactive oxygen species (ROS) production. The effects of albumin on EC activation were tested using circulating factors elevated in DC (lipopolysaccharide (LPS), tumour necrosis factor- α (TNFα), bilirubin). Results: Mitochondrial morphology distinguished ECs exposed to DC plasma from those exposed to CC or HC plasma. Albumin supplementation shifted EC morphology towards a healthier phenotype. ECs exposed to DC plasma showed increased mito chondrial respiration without a concomitant increase in ROS production, which was normalised by albumin. Albumin had no significant effects on EC activation induced by circulating factors. Conclusions: Plasma from patients with DC and hypoalbuminemia induces EC morphological changes, particularly in mito chondria. Albumin mitigates these effects, suggesting a direct modulatory role on mitochondrial function and supporting its therapeutic potential in vascular dysfunction in cirrhosis.
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Albumin restores endothelial cell mitochondrial morphology in patients with decompensated cirrhosis