Macrophage foam-cell formation in streptozotocin-induced diabetic mice: stimulatory effect of glucose.
BACKGROUND
Diabetes is associated with an increased risk for atherosclerosis. We investigated the effect of diabetes induction on atherogenesis and on macrophage-foam cell formation.


RESULTS
Atherosclerotic apolipoprotein-E-deficient mice were converted into diabetic mice by streptozotocin injection. Aortic atherosclerotic lesion area was significantly enhanced by 67% and 106% in mice that were diabetic for 1 and 3 months, respectively, compared to the non-diabetic mice. Moreover, mouse peritoneal macrophages (MPM) from diabetic mice for 1 and 3 months exhibit higher lipid peroxides content by 55% and 63%, respectively, in association with the MPM glucose content. Oxidized LDL (Ox-LDL) uptake by MPM obtained from diabetic mice for 1 and 3 months was significantly increased by 36% and 45%, respectively, in association with the increased macrophage cholesterol content. To determine whether the accelerated foam cell formation in diabetic mice could result from a direct effect of glucose on macrophages, J-774-A.1 macrophages were incubated with increasing glucose concentrations (2.5-62 mM). Glucose-enriched macrophages exhibit dose-dependent higher peroxides content up to 7.5-fold and increased Ox-LDL cellular uptake associated with up-regulation of the scavenger receptor CD36 at the mRNA level.


CONCLUSIONS
Induction of diabetes in atherosclerotic mice led to an accelerated atherosclerosis and macrophage-derived foam cell formation, probably by involving a glucose-dependent related mechanism.
Hayek
Tony
T
The Lipid Research Laboratory, The Bruce Rappaport Faculty of Medicine, Technion, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, 31096 Haifa, Israel. t_hayek@rambam.health.gov.il
Hussein
Khitam
K
Aviram
Michael
M
Coleman
Raymond
R
Keidar
Shlomo
S
Pavoltzky
Elsa
E
Kaplan
Marielle
M
D000818:Animals; D001018:Aortic Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001057:Apolipoproteins E / Q000172:deficiency; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D018955:CD36 Antigens / Q000096:biosynthesis / Q000235:genetics; D002478:Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000473:pathology*; D005487:Foam Cells / Q000473:pathology*; D005947:Glucose / Q000494:pharmacology*; D006938:Hyperlipoproteinemia Type II / Q000235:genetics; D015227:Lipid Peroxidation; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000096:biosynthesis; D011897:Random Allocation; D013311:Streptozocin; D013481:Superoxides / Q000378:metabolism
D001057:Apolipoproteins E; D018955:CD36 Antigens; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; C099252:oxidized low density lipoprotein; D013481:Superoxides; D013311:Streptozocin; D002784:Cholesterol; D005947:Glucose