The Liver-Vascular Axis in Metabolic Dysfunction-Associated Steatotic Liver Disease: Pathogenic Pathways and Emerging Targets

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disorder globally and is increasingly recognized as a key contributor to cardiovascular disease (CVD). The association between MASLD and CVD extends beyond shared risk factors such as obesity, type 2 diabetes, and dyslipidemia, indicating direct pathogenic interactions along the liver-vascular axis. MASLD is linked to subclinical atherosclerosis, cardiac remodeling, arrhythmias, and major adverse cardiovascular events. However, although CVD is a leading cause of death in MASLD, its independent contribution to cardiovascular mortality after adjustment for traditional risk factors remains controversial. This review examines the underlying mechanisms connecting MASLD and vascular dysfunction, including visceral adiposity, chronic low-grade inflammation, oxidative stress, endothelial dysfunction, insulin resistance, and postprandial hyperlipidemia. Hepatokines, lipotoxicity, and gut-derived metabolites are emerging mediators of vascular injury. Given the global burden of MASLD, heightened awareness of its cardiovascular implications is essential. Early identification of high-risk individuals and targeted interventions may help reduce cardiovascular morbidity and mortality. Further research is needed to clarify causal pathways and support the development of diagnostic and therapeutic interventions focused on the liver-vascular interface.