METRNL levels decrease in mice and humans with atherosclerosis. (A, B) Different extents of atherosclerosis are produced in one-year-old ApoE–/– mice, with more severe atherosclerosis in ApoE–/– mice fed high fat diet (HFD, for 22 weeks) than normal chow (A). Serum METRNL levels are reduced in ApoE–/– mice, with more reduction in ApoE–/– mice fed HFD than normal chow (B). n = 4–5. (C) METRNL and CD31 in the endothelium of aortae from normal control and ApoE–/– mice. Endothelial METRNL decreases in ApoE–/– mice, with obvious lack of endothelial METRNL in the region of atherosclerotic lesion (AS). Bar = 20 μm. Three independent experiments performed. (D) Plasma levels of cardiac troponin Ι (cTn Ι) and METRNL in control (n = 11) and myocardial infarction (MI) patients with atherosclerosis (AS) (n = 21). (E) Serum METRNL levels in mice 24 h after myocardial infarction (MI) produced by coronary artery ligation surgery (right). n = 10. Two independent experiments performed. Electrocardiograms of mice immediately after the surgery (left), and 2,3,5-triphenyltetrazolium chloride-stained heart sections 24 h after the surgery (middle) are shown. Sham: sham operation. Data are mean ± SEM. ∗P < 0.05, #P < 0.05, ∗∗∗P < 0.001 by two-tailed Student's t test in (D) and one-way ANOVA followed by two-tailed Student's t test in (B). ∗P < 0.05 vs. C57; #P < 0.05 vs. ApoE–/–.