(A) Strategy to test liver regeneration in mice with genetic depletion of ApoM (Apom^-/-). Both Apom^-/- and wild-type (WT) control mice were subjected to surgical resection of 70% liver mass (partial hepatectomy, PH). To perform PH, three most anterior lobes (right medial, left medial and left lateral lobes) (which comprise 70% of the liver weight) were resected without injuring the blood supply to the caudate and the right lobes. Restoration of functional liver mass and vascular architecture after PH was analyzed in both mouse genotypes. Histological analysis of the liver from WT and Apom^-/- mice after sham operation is shown in Supplemental Figure 1A. (B–G) Recovery of liver weight (B), body weight (C), mouse survival rate (D), restoration of hepatic function (E), and extent of liver parenchymal injury (F and G) in Apom^-/- and WT mice at indicated time points after PH. Levels of plasma bilirubin and serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were measured to examine hepatic function and liver damage. N = 6-8 mice per group. Each dot in the dot plot indicates individual animal throughout all figures. Statistical difference was determined by One way ANOVA throughout Figure 1. (H and I) Sinusoidal vascular regeneration in hepatectomized mice. Expression of VEGFR3, a specific marker of liver sinusoidal endothelial cell (LSEC) was tested by immunostaining. To examine functional sinusoidal vessels that are perfused, 2 mg/kg B4-Isolectin binding to endothelial cell surface was intravenously (i.v.) injected into the mice after PH. Representative image of immunostaining is shown in H, and percentage of VEGFR3⁺ and isolectin⁺ vascular area was quantified in (I). Note the increased lumen size in non-perfused isolectin^-VEGFR3⁺ liver sinusoidal vasculature of Apom^-/- mice after PH. N = 5 mice per group. Scale bar = 50 μm.