Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy.
The differentiation of macrophages into cytokine-secreting foam cells plays a critical role in the development of diabetic angiopathy. J774.1, a murine macrophage cell line, reportedly differentiates into foam cells when incubated with oxidized LDL, ApoE-rich VLDL or WHHLMI (myocardial infarction-prone Watanabe heritable hyperlipidemic) rabbit serum. In this study, serum samples from Type 2 diabetic patients were added to the medium with J774.1 cells and the degree of foam cell induction was quantified by measuring lipid accumulation. These values were calculated relative to the activities of normal and WHHLMI rabbit sera as 0% and 100%, respectively, and termed the MMI (Macrophage Maturation Index). These MMI values reflected intracellular lipids, including cholesteryl ester assayed by GC/MS. Statistical analysis revealed MMI to correlate positively and independently with serum triglycerides, the state of diabetic retinopathy, nephropathy and obesity, but negatively with administration of alpha-glucosidase inhibitors or thiazolidinediones. Taken together, our results suggest that this novel assay may be applicable to the identification of patients at risk for rapidly progressive angiopathic disorders.
Cui
Xinglong
X
Department of Medical Chemistry, Division of Molecular Medical Science, Graduate School of Biomedical Science, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima, Japan.
Kushiyama
Akifumi
A
Yoneda
Masayasu
M
Nakatsu
Yusuke
Y
Guo
Ying
Y
Zhang
Jun
J
Ono
Haruya
H
Kanna
Machi
M
Sakoda
Hideyuki
H
Ono
Hiraku
H
Kikuchi
Takako
T
Fujishiro
Midori
M
Shiomi
Masashi
M
Kamata
Hideaki
H
Kurihara
Hiroki
H
Kikuchi
Masatoshi
M
Kawazu
Shoji
S
Nishimura
Fusanori
F
Asano
Tomoichiro
T
D000818:Animals; D001794:Blood Pressure; D015992:Body Mass Index; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D003925:Diabetic Angiopathies / Q000097:blood*; D005260:Female; D005487:Foam Cells / Q000502:physiology*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007958:Leukocyte Count; D008055:Lipids / Q000097:blood / Q000302:isolation & purification; D008075:Lipoproteins, HDL / Q000097:blood; D008077:Lipoproteins, LDL / Q000494:pharmacology; D008111:Liver Function Tests; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D008297:Male; D051379:Mice; D011817:Rabbits; D012044:Regression Analysis
D006442:Glycated Hemoglobin; D008055:Lipids; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein