An aldose reductase inhibitor prevents the glucose-induced increase in PDGF-beta receptor in cultured rat aortic smooth muscle cells.
To examine the role of platelet-derived growth factor (PDGF) and the polyol pathway in the growth activity of smooth muscle cells (SMCs), [(3)H]-thymidine incorporation, [(125)I]-PDGF-BB binding and expression of PDGF-beta receptor protein were measured in rat aortic SMCs cultured with 5.5 or 20 mM glucose with or without anti-PDGF antibody or an aldose reductase inhibitor, epalrestat. SMCs cultured with 20 mM glucose demonstrated an accelerated thymidine incorporation compared with SMCs cultured with 5.5 mM glucose, which was prevented by anti-PDGF antibody. This acceleration of growth activity by 20 mM glucose was accompanied by an increase in PDGF-BB binding, which was due to the increased number of PDGF-beta receptors and the overexpression of PDGF-beta receptor protein. Epalrestat prevented all these abnormalities. These observations suggest that polyol pathway hyperactivity plays an important role in the proliferation of SMCs which may be mediated through the accelerated expression of PDGF-beta receptor protein.
Kasuya
Y
Y
The Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, 466-8550, Japan.
Nakamura
J
J
Hamada
Y
Y
Nakayama
M
M
Sasaki
H
H
Komori
T
T
Chaya
S
S
Watanabe
G
G
Naruse
K
K
Nakashima
E
E
Kato
K
K
Hotta
N
N
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001011:Aorta / Q000378:metabolism; D000077214:Becaplermin; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007294:Inositol / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D020574:Proto-Oncogene Proteins c-sis; D051381:Rats; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism*; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013012:Sorbitol / Q000378:metabolism; D053778:Thiazolidines
D000906:Antibodies; D004791:Enzyme Inhibitors; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D053778:Thiazolidines; D000077214:Becaplermin; D005632:Fructose; C038131:epalrestat; D007294:Inositol; D013012:Sorbitol; D012236:Rhodanine; D004247:DNA; D000449:Aldehyde Reductase; D017479:Receptors, Platelet-Derived Growth Factor; D005947:Glucose