[Advanced glycation end products accelerate atherosclerosis via enhancement of oxidative stress].
OBJECTIVE
To investigate the effect of advanced glycation end products (AGE) on atheromatous plaque formation and its possible mechanisms.


METHODS
Fifty rabbits were randomly divided into five groups of 10 rabbits: group A, fed with hypercholesterolemic diet and injected intravenously with AGE modified rabbit serum albumin (AGE-RSA); group B, fed with hypercholesterolemic diet and injected with unmodified RSA; group C, fed with hypercholesterolemic diet; group D, fed with normal diet alone: and group E, fed with normal diet and injected with AGE-RSA. Ten weeks after the rabbits were killed. Their aortas were taken out and stained with Sudan red IV. The extent of atheromatous plaques in the aortas en face was evaluated by computer-assisted morphometry and by histologic examination. Photoshop system was used to measure the percentage of atheromatous plaques in the area of tunica intima. The depositions of AGE, malondialdehyde modified low-density lipoprotein (MDA-LDL), oxidized low-density lipoprotein (ox-LDL) and expression of receptor of AGE (RAGE) in aortic tissue were detected by using immunohistological staining. The circulating AGE, blood lipids, serum selenium glutathione peroxydase (SeGSHPx) activity, malonyldialdehyde (MDA), and oxidized LDL (ox-LDL) were detected before the experiment and after the rabbits were killed.


RESULTS
(1) The relative plaque area was significantly increased in group A (50% +/- 8%) compared with in group B (21% +/- 7%) and group C (29% +/- 6%). No plaque could be found in animals fed with normal diet (group D) even in those receiving repeated injections of AGE-RSA (group E). Depositions of ox-LDL, MDA-LDL and AGE in atherosclerotic lesions increased and RAGE expression were upregulated in the rabbits fed with hypercholesterolemic diet and injected with AGE-RSA (group A) compared with the other four groups. (2) All hypercholesterolemic rabbits showed comparable serum levels of triglyceride and cholesterol. However, the serum levels of AGE, ox-LDL and MDA were significantly higher and the serum level of SeGSHPx was relatively lower in group A compared with those in the other four groups. (3) The serum level of AGE was directly correlated with the serum ox-LDL (r = 0.459, P < 0.01) or serum MDA concentration (r = 0.423, P < 0.05), and inversely correlated with the serum level of SeGSHPx (r = - 0.448, P < 0.01). A close correlation was found between the serum level of AGE and endothelium RAGE expression (r = 0.384, P < 0.05) and deposition area of AGE (r = 0.468, P < 0.05) in aorta.


CONCLUSIONS
AGE accelerates the atheromatous plaque formation through induction of oxidative stress and upregulation of RAGE.
Zhang
Wei-Ru
WR
Department of Nephrology, Nanfang Hospital, Guangzhou 510515, China.
Hou
Fan-Fan
FF
Liu
Shang-Xi
SX
Guo
Zhi-Jian
ZJ
Zhou
Zhan-Mei
ZM
Wang
Guo-Bao
GB
Fu
Ning
N
Liu
Zhi-Qiang
ZQ
Wang
Li
L
Zhou
Mei
M
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology*; D002791:Cholesterol, Dietary / Q000633:toxicity; D004036:Diet, Atherogenic; D017127:Glycation End Products, Advanced / Q000097:blood / Q000633:toxicity*; D006937:Hypercholesterolemia / Q000150:complications*; D008055:Lipids / Q000097:blood; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D011817:Rabbits; D011897:Random Allocation; D017382:Reactive Oxygen Species / Q000378:metabolism
D002791:Cholesterol, Dietary; D017127:Glycation End Products, Advanced; D008055:Lipids; D017382:Reactive Oxygen Species