Inhibition of endothelial cell differentiation on a glycosylated reconstituted basement membrane complex.
The vascular basement membrane is involved in the regulation of endothelial cell differentiation. The accumulation of advanced glycosylation endproducts (AGEs) has been demonstrated on these basement membranes in patients with diabetes. We examined the effect of AGEs on endothelial cell behavior on reconstituted basement membrane, Matrigel. Human umbilical vein-derived endothelial cells (HUVECs) stopped proliferating and differentiated into capillary-like tube-shaped structures on Matrigel. Laminin antibody partially blocked this process. HUVECs cultured on glycosylated Matrigel, however, proliferated and formed a monolayer without tube formation. The inclusion of aminoguanidine, an inhibitor of AGE formation, during the glycosylation of Matrigel restored HUVEC differentiation. Although the laminin adsorbed onto the plastic culture wells promoted HUVEC attachment and spreading, glycosylated laminin reduced HUVEC attachment by 50% and abolished cellular spreading. These effects were restored by aminoguanidine. HUVEC attachment to glycosylated laminin was further reduced by AGE-modified albumin, poly I, acetylated low-density lipoprotein, or maleylated albumin, ligands for a scavenger receptor. Coating the culture dishes with the laminin peptides RGD, YIGSR, and SIKVAV supported the attachment of HUVECs that was unaffected by glycosylation. Results suggest that AGE accumulation on the basement membranes inhibits endothelial cell differentiation by impairing the normal interactions of endothelial cell receptors with their specific matrix ligands. This process may be involved in diabetic angiopathy.
Kuzuya
M
M
Department of Geriatrics, Nagoya University School of Medicine, Japan.
Satake
S
S
Miura
H
H
Hayashi
T
T
Iguchi
A
A
D000418:Albumins / Q000494:pharmacology; D000595:Amino Acid Sequence; D001485:Basement Membrane / Q000166:cytology / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D003094:Collagen; D004338:Drug Combinations; D004730:Endothelium, Vascular / Q000166:cytology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D017127:Glycation End Products, Advanced; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007797:Laminin / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000378:metabolism; D011069:Poly I / Q000494:pharmacology; D011509:Proteoglycans; D011971:Receptors, Immunologic / Q000378:metabolism; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; D051122:Scavenger Receptors, Class B; D012710:Serum Albumin, Bovine; D014471:Umbilical Veins
D000418:Albumins; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D017127:Glycation End Products, Advanced; D006146:Guanidines; D007797:Laminin; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; D009842:Oligopeptides; D011509:Proteoglycans; D011971:Receptors, Immunologic; D018110:Receptors, Lipoprotein; D051116:Receptors, Scavenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; C049877:maleylalbumin; C059485:matrigel; D011069:Poly I; D012710:Serum Albumin, Bovine; D003094:Collagen; C004479:pimagedine