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-HDL appears to be important in transendothelial HDL transport and cholesterol efflux. Clinical and preclinical studies have linked reduced ApoM expression with cardiometabolic diseases, such as obesity, insulin resistance, type 2 diabetes, and chronic kidney disease, while emerging evidence also implicates ApoM in neurovascular, inflammatory, and retinal disorders. ApoM expression and plasma levels are regulated by hepatocyte nuclear factors, Forkhead box O nuclear transcription factors and inflammatory cytokines but also pharmacologically by statins and SGLT2 inhibitors. Recent development of engineered ApoM-based biologics, such as ApoM-Fc and ApoA1-ApoM fusion proteins, shows promise in preclinical models of vascular disease, demonstrating improvements in endothelial function, inflammation, and pathological neovascularization without inducing immunosuppression or bradycardia. Collectively, these insights position ApoM as both a critical biomarker and a therapeutic target for vascular health. Advancing ApoM-based therapies may offer a novel precision medicine strategy to treat cardiovascular and metabolic diseases through endothelial-targeted modulation of S1P signaling.
Dorweiler et al. (Sat,) studied this question.