Lipotoxicity-driven vascular alterations and angiogenesis are central to the progression of MASLD and the development of portal hypertension.
BACKGROUND: Chronic liver diseases (CLDs), particularly metabolic-associated steatotic liver disease (MASLD), represent a significant global health burden, with potential progression to fibrosis, portal hypertension, and hepatocellular carcinoma (HCC). This review explores the role of vascular remodeling and angioarchitecture in MASLD pathogenesis, emphasizing the importance of microvascular changes, endothelial dysfunction, and angiogenesis in disease progression. Hepatic steatosis leads to hepatocyte enlargement and sinusoidal compression, disrupting microcirculation and oxygenation. Lipotoxicity, which is driven by excess fatty acids and oxidative stress, triggers inflammation and vascular permeability, fostering a proangiogenic environment. Capillarization of liver sinusoidal endothelial cells (LSECs) and activation of hepatic stellate cells (HSCs) contribute to fibrosis and neovascularization. Angiogenesis, especially via VEGF and other cytokines, is implicated in the transition from steatosis to steatohepatitis (MASH) and ultimately HCC, even in non-cirrhotic livers. Notably, portal hypertension may develop early in MASLD, independent of cirrhosis. Given the central role of vascular alterations in MASLD, future therapies may target endothelial and stromal cell interactions. Further research is needed to delineate disease-specific mechanisms and their implications for fibrosis and carcinogenesis.
Hirayama et al. (Wed,) studied this question.