title: Transcriptional analysis of the endothelial response to diabetes reveals a role for galectin-3.
abstract: To characterize the endothelial dysfunction associated with Type II diabetes, we surveyed transcriptional responses in the vascular endothelia of mice receiving a diabetogenic, high-fat diet. Tie2-GFP mice were fed a diet containing 60% fat calories (HFD); controls were littermates fed normal chow. Following 4, 6, and 8 wk, aortic and leg muscle tissues were enzymatically dispersed, and endothelial cells were obtained by fluorescence-activated cell sorting. Relative mRNA abundance in HFD vs. control endothelia was measured with long-oligo microarrays; highly dysregulated genes were confirmed by real-time PCR and protein quantification. HFD mice were hyperglycemic by 2 wk and displayed vascular insulin resistance and decreased glucose tolerance by 5 and 6 wk, respectively. Endothelial transcripts upregulated by HFD included galectin-3 (Lgals3), 5-lipoxygenase-activating protein, and chemokine ligands 8 and 9. Increased LGALS3 protein was detected in muscle endothelium by immunohistology accompanied by elevated LGALS3 in the serum of HFD mice. Our comprehensive analysis of the endothelial transcriptional response in a model of Type II diabetes reveals novel regulation of transcripts with roles in inflammation, insulin sensitivity, oxidative stress, and atherosclerosis. Increased endothelial expression and elevated humoral levels of LGALS3 supports a role for this molecule in the vascular response to diabetes, and its potential as a direct biomarker for the inflammatory state in diabetes.
authors.affiliation: Center for Cardiovascular Research, University of Hawaii John A. Burns School of Medicine, Honolulu, Hawaii 96813, USA.
authors.forename: April L
authors.initials: AL
authors.lastname: Darrow
authors.forename: Ralph V
authors.initials: RV
authors.lastname: Shohet
authors.forename: J Gregory
authors.initials: JG
authors.lastname: Maresh
mesh_terms: D000818:Animals; D002469:Cell Separation; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000235:genetics*; D059305:Diet, High-Fat; D004703:Endocrine System / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism / Q000473:pathology; D004727:Endothelium / Q000378:metabolism* / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D037502:Galectin 3 / Q000097:blood / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D042787:Receptor, TIE-2; D014158:Transcription, Genetic
chemical_list: D037502:Galectin 3; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; C079086:Tek protein, mouse