Mechanisms involved in the stimulatory effect of advanced glycation end products on growth of rat aortic smooth muscle cells.
Hyperglycemia is an important cause of accelerated atherosclerosis in diabetic patients. We examined the effect of hyperglycemia and advanced glycation end products (AGE) on proliferation of rat aortic smooth muscle cells (SMC) in culture; in vivo, this event is believed to contribute importantly to atherogenesis in diabetes mellitus. Glucose itself dose-dependently inhibited thymidine uptake by SMC, but AGE increased thymidine uptake, suggesting that SMC proliferation is accelerated by AGE. To examine possible mechanisms for this effect, we studied nuclear factor-kappa B (NF-kappaB) activation and the tyrosine phosphorylation pathway; AGE stimulated NF-kappaB activity, but phosphorylation of the platelet-derived growth factor (PDGF) receptor was unchanged. In Chinese hamster ovary (CHO) cells overexpressing galectin-3, an AGE receptor related to atherosclerosis, AGE increased thymidine uptake. This suggests SMC proliferation is enhanced by AGE via galectin-3. As pathways involving AGE-galectin-3 interaction thus may be involved in macroangiopathy, AGE appears to be important to the role of SMC in accelerated atherosclerosis associated with diabetes mellitus.
Seki
N
N
Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, Japan.
Hashimoto
N
N
Sano
H
H
Horiuchi
S
S
Yagui
K
K
Makino
H
H
Saito
Y
Y
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects; D001161:Arteriosclerosis / Q000473:pathology; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D016466:CHO Cells; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D024202:Electrophoretic Mobility Shift Assay; D037502:Galectin 3 / Q000235:genetics / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D011921:Rats, Inbred WKY; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013268:Stimulation, Chemical; D013936:Thymidine / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism
D001786:Blood Glucose; D037502:Galectin 3; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D012710:Serum Albumin, Bovine; D014443:Tyrosine; D020797:Receptor, Platelet-Derived Growth Factor beta; D013936:Thymidine