Endothelial dysfunction is a risk factor for lipid metabolism disorders: underlying mechanisms and potential...

Lipid homeostasis and vascular endothelial function are fundamental to cardiovascular health. This review systematically outlines the regulatory mechanisms that maintain the dynamic balance between the endothelium and systemic lipid metabolism, emphasizing the endothelium as an active regulator. The endothelium influences lipid metabolism in multiple organs by regulating vascular tone, angiogenesis, barrier integrity, and inflammatory response. Studies have demonstrated that genetic ablation of endothelial-specific genes disrupts lipid metabolism in key metabolic organs, including the liver, adipose tissue, and skeletal muscle. This impairment of endothelial function may result in obesity, insulin resistance, hyperlipidemia, and MASLD/MASH. The specific mechanisms linking endothelial dysfunction to systemic lipid metabolism are highlighted. This review clarifies the progression of systemic lipid metabolism disorders driven by an imbalance in the "endothelial-lipid metabolism homeostasis axis". Potential therapeutic strategies targeting this axis for lipid-metabolism disorders and related cardiovascular diseases are also discussed.