title: Effect of high glucose on formation of extracellular matrix components by cultured rat heart endothelial cells.
abstract: In an attempt to define the basis for the microvascular changes observed in diabetic myocardium, a study was undertaken on the effect of elevated glucose on the synthesis by rat heart endothelial cells of the extracellular matrix components, types VI, IV and I collagen, as well as fibronectin. Confluent cultures of these cells, isolated by fluorescence-activated cell sorting after treatment with rhodamine-labelled acetylated low density lipoprotein, showed a three to fivefold enhancement in the synthesis of type VI collagen after exposure for 48 h to high glucose (20 to 30 mmol/l), as determined by immunoblot analysis. Increased production of type IV collagen and fibronectin was also observed, but the change was smaller and no effect on type I collagen was found. Measurement of mRNA levels by hybridization with cDNA probes indicated that 48-h exposure to high glucose significantly increased the level of transcripts for type VI and IV collagens but not for type I collagen. While glucose consumption by endothelial cells in high glucose doubled in the initial 24-h period, utilization returned to normal by 48 h, concomitant with a reduction in GLUT1 transcript levels, suggesting that signals for stimulation of collagen synthesis must be active during the initial period of exposure to elevated glucose levels.
authors.affiliation: Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Spiro
authors.forename: Q
authors.initials: Q
authors.lastname: He
authors.forename: M L
authors.initials: ML
authors.lastname: D'Autilia
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D018076:DNA, Complementary; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis*; D005353:Fibronectins / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D051272:Glucose Transporter Type 1; D006321:Heart; D015151:Immunoblotting; D007700:Kinetics; D046911:Macromolecular Substances; D009004:Monosaccharide Transport Proteins / Q000032:analysis / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D051381:Rats; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D051272:Glucose Transporter Type 1; D046911:Macromolecular Substances; D009004:Monosaccharide Transport Proteins; D012333:RNA, Messenger; C495679:Slc2a1 protein, rat; D003094:Collagen; D005947:Glucose