Effect of glycated collagen on proliferation of human smooth muscle cells in vitro.
While non-enzymatic glycation of long-lived tissue proteins such as collagen has been implicated in chronic complications of diabetes mellitus, its role in the aetiology of diabetic macroangiopathy has not been elucidated. To test the hypothesis that glycation of collagen abolishes the inhibitory effect of native collagen on the proliferation of human smooth muscle cells, we obtained smooth muscle cells from human gastric arteries and cultured them on dishes coated with glycated or non-glycated collagen. The proliferation of human smooth muscle cells in the presence of 10% fetal calf serum or platelet derived growth factor-BB (10 ng/ml) was inhibited by type 1 collagen coated on the dishes. Glycation of collagen with glucose 6-phosphate for 7 days abolished the growth-inhibitory effect of native collagen. Succinylation of collagen, which like glycation blocked the lysyl residues in collagen, also abolished the growth-inhibitory effect. Adhesion of human smooth muscle cells to collagen-coated dishes was not affected by glycation of collagen. Addition of glycated albumin to the medium did not affect the growth of human smooth muscle cells on plastic dishes. The inhibition of human smooth muscle cell proliferation by collagen was not reversed by the glycation of collagen in the presence of aminoguanidine. Results suggest that early glycation abolishes the inhibitory effect of collagen on human smooth muscle cell proliferation and may thus participate in the progression of macro-angiopathy in diabetes.
Iino
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyusyu University, Fukuoka, Japan.
Yoshinari
M
M
Yamamoto
M
M
Kaku
K
K
Doi
Y
Y
Ichikawa
K
K
Iwase
M
M
Fujishima
M
M
D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000032:analysis / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000037:antagonists & inhibitors; D006031:Glycosylation; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D013387:Succinic Anhydrides / Q000737:chemistry; D013936:Thymidine / Q000032:analysis / Q000378:metabolism; D014316:Tritium
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D010982:Platelet-Derived Growth Factor; D013387:Succinic Anhydrides; D014316:Tritium; C031801:succinic anhydride; D003094:Collagen; C004479:pimagedine; D013936:Thymidine