title: Haploinsufficiency of E-selectin ligand-1 is associated with reduced atherosclerotic plaque macrophage content while complete deficiency leads to early embryonic lethality in mice.
abstract: 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.
authors.affiliation: Department of Internal Medicine, Cardiovascular Research Center, University of Michigan, 7301A MSRB III, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0644, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Chiao
authors.initials: C
authors.lastname: Guo
authors.forename: Jintao
authors.initials: J
authors.lastname: Wang
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Kwak
authors.forename: Kristina L
authors.initials: KL
authors.lastname: Bahrou
authors.forename: Daniel T
authors.initials: DT
authors.lastname: Eitzman
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism* / Q000473:pathology; D001018:Aortic Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D003094:Collagen / Q000378:metabolism; D004195:Disease Models, Animal; D020964:Embryo Loss / Q000235:genetics / Q000378:metabolism*; D005838:Genotype; D005865:Gestational Age; D057895:Haploinsufficiency; D006579:Heterozygote; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D058226:Plaque, Atherosclerotic; D017468:Receptors, Fibroblast Growth Factor / Q000172:deficiency* / Q000235:genetics; D012795:Sialoglycoproteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D001057:Apolipoproteins E; D017468:Receptors, Fibroblast Growth Factor; D012795:Sialoglycoproteins; C086711:cysteine-rich fibroblast growth factor receptor; D003094:Collagen