Haploinsufficiency of E-selectin ligand-1 is associated with reduced atherosclerotic plaque macrophage content while complete deficiency leads to early embryonic lethality in mice

E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/−) were intercrossed to produce ESL-1−/− mice, however ESL-1−/− mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE−/−), ESL-1+/− mice were generated and fed western diet. Compared to ApoE−/−, ESL-1+/+ mice, atherosclerotic lesions from ApoE−/−, ESL-1+/− contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality.