A comparative study of cultured smooth muscle cell proliferation and injury, utilizing glycated low density lipoproteins with slight oxidation, auto-oxidation, or extensive oxidation.
We investigated the influence of glycated low density lipoprotein (LDL) for vascular smooth muscle cell (SMC) proliferation or injury. We utilized glycated, slightly oxidized LDL (GLDL-LOX), glycated, auto-oxidized LDL (GLDL) and glycated, metal-induced extensively oxidized LDL (GLDL-OX) to examine the effect of glycation itself or combined glycation and oxidation on SMC. GLDL-LOX induced SMC proliferation and migration, and increased the number of platelet-derived growth factor receptor, beta subunits, (PDGF-R) positive SMC. Also, GLDL-LOX promoted protease activity, compared with the other groups including native LDL (control). GLDL and GLDL-OX demonstrated SMC injury with apoptosis and Bax protein expression, compared with native LDL and GLDL-LOX. These results suggested that LDL glycation contributed to the progression of atherosclerosis by promoting SMC migration and proliferation, with little dependence on oxidative modification. Secondary auto-oxidation adding to glycation induced SMC apoptosis, and SMC injury occurred in the state of strong oxidation with glycation. We concluded that LDL glycation might play a key role in the progression of atherosclerosis in diabetes, and glycated LDL promoted atherosclerosis, even with little assistance from oxidation.
Taguchi
S
S
Department of Pathology, Nihon University, School of Medicine, Tokyo, Japan.
Oinuma
T
T
Yamada
T
T
D017209:Apoptosis / Q000187:drug effects; D001161:Arteriosclerosis / Q000209:etiology; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003925:Diabetic Angiopathies / Q000209:etiology; D010450:Endopeptidases / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007150:Immunohistochemistry; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects* / Q000293:injuries; D010084:Oxidation-Reduction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D017479:Receptors, Platelet-Derived Growth Factor / Q000378:metabolism; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D008077:Lipoproteins, LDL; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; C099252:oxidized low density lipoprotein; D017479:Receptors, Platelet-Derived Growth Factor; D010450:Endopeptidases