Effect of high glucose on formation of extracellular matrix components by cultured rat heart endothelial cells.
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.
Spiro
M J
MJ
Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
He
Q
Q
D'Autilia
M L
ML
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
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