Right ventricular failure (RVF) is a robust predictor of mortality in pulmonary arterial hypertension (PAH); however, the mechanisms linking RVF to end-organ dysfunction remain unclear. Hepatic impairments portend poor outcomes in PAH, but the cell-specific effects of PAH on the human liver are unknown. Here, we performed single nucleus RNA sequencing on autopsy-derived liver tissue from five PAH patients and four non-PAH controls and compared these findings to non-alcoholic steatohepatitis (NASH) and Fontan-associated liver disease (FALD). PAH hepatocytes were characterized by a pro-proliferative, Warburg-like metabolic phenotype. PAH endothelial cells (ECs) also adopted a Warburg-like profile. Although EC PI3K-Akt activation was present in PAH and FALD ECs, only PAH ECs demonstrated impaired adhesion/barrier signaling. In PAH hepatic stellate cells (HSCs), PI3K-Akt signaling was enriched, while NASH and FALD HSCs co-activated PI3K-Akt and TGF-
- Blake, M. J.
- Prins, S. E.
- Blake, J. C.
- Hartweck, L. M.
- Mendelson, J. B.
- Provencher, S.
- Breuils-Bonnet, S.
- Bonnet, S.
- Prins, K. W.
