Vascular and inflammatory stresses mediate atherosclerosis via RAGE and its ligands in apoE-/- mice

被引:303
作者
Harja, Evis [1 ]
Bu, De-Xiu [1 ]
Hudson, Barry I. [1 ]
Chang, Jong Sun [1 ]
Shen, Xiaoping [1 ]
Hallam, Kellie [1 ]
Kalea, Anastasia Z. [1 ]
Lu, Yan [1 ]
Rosario, Rosa H. [1 ]
Oruganti, Sai [1 ]
Nikolla, Zana [1 ]
Belov, Dmitri [1 ]
Lalla, Evanthia [2 ]
Ramasamy, Ravichandran [1 ]
Yan, Shi Fang [1 ]
Schmidt, Ann Marie [1 ]
机构
[1] Columbia Univ, Med Ctr, Dept Surg, Div Surg Sci, New York, NY 10032 USA
[2] Columbia Univ, Med Ctr, Coll Dent Med, New York, NY USA
关键词
D O I
10.1172/JCI32703
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Endothelial dysfunction is a key triggering event in atherosclerosis. Following the entry of lipoproteins into the vessel wall, their rapid modification results in the generation of advanced glycation endproduct epitopes and subsequent infiltration of inflammatory cells. These inflammatory cells release receptor for advanced glycation endproduct (RAGE) ligands, specifically S100/calgranulins and high-mobility group box 1, which sustain vascular injury. Here, we demonstrate critical roles for RAGE and its ligands in vascular inflammation, endothelial dysfunction, and atherosclerotic plaque development in a mouse model of atherosclerosis, apoE(-/-) mice. Experiments in primary aortic endothelial cells isolated from mice and in cultured human aortic endothelial cells revealed the central role of JNK signaling in transducing the impact of RAGE ligands on inflammation. These data highlight unifying mechanisms whereby endothelial RAGE and its ligands mediate vascular and inflammatory stresses that culminate in atherosclerosis in the vulnerable vessel wall.
引用
收藏
页码:183 / 194
页数:12
相关论文
共 47 条
[1]   Production of Nε-(carboxymethyl)lysine is impaired in mice deficient in NADPH oxidase -: A role for phagocyte-derived oxidants in the formation of advanced glycation end products during inflammation [J].
Anderson, MM ;
Heinecke, JW .
DIABETES, 2003, 52 (08) :2137-2143
[2]  
Asahi K, 2000, KIDNEY INT, V58, P1780, DOI 10.1111/j.1523-1755.2000.00340.x
[3]  
BOBRYSHEV YV, 1995, CARDIOVASC RES, V29, P689, DOI 10.1016/0008-6363(96)88642-1
[4]   Decreased lesion formation in CCR2-/- mice reveals a role for chemokines in the initiation of atherosclerosis [J].
Boring, L ;
Gosling, J ;
Cleary, M ;
Charo, IF .
NATURE, 1998, 394 (6696) :894-897
[5]   RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice [J].
Bucciarelli, LG ;
Wendt, T ;
Qu, W ;
Lu, Y ;
Lalla, E ;
Rong, LL ;
Goova, MT ;
Moser, B ;
Kislinger, T ;
Lee, DC ;
Kashyap, Y ;
Stern, DM ;
Schmidt, AM .
CIRCULATION, 2002, 106 (22) :2827-2835
[6]   RAGE limits regeneration after massive liver injury by coordinated suppression TNF-α and NF-κB [J].
Cataldegirmen, G ;
Zeng, S ;
Feirt, N ;
Ippagunta, N ;
Dun, H ;
Lu, Y ;
Rong, LL ;
Hofmann, MA ;
Kislinger, T ;
Pachydaki, SI ;
Jenkins, DG ;
Weinberg, A ;
Lefkowitch, J ;
Rogiers, X ;
Yan, SF ;
Schmidt, AM ;
Emond, JC .
JOURNAL OF EXPERIMENTAL MEDICINE, 2005, 201 (03) :473-484
[7]   Blockade of late stages of autoimmune diabetes by inhibition of the receptor for advanced glycation end products [J].
Chen, YL ;
Yan, SSD ;
Colgan, J ;
Zhang, HP ;
Luban, J ;
Schmidt, AM ;
Stern, D ;
Herold, KC .
JOURNAL OF IMMUNOLOGY, 2004, 173 (02) :1399-1405
[8]   ENDOTHELIAL EXPRESSION OF A MONONUCLEAR LEUKOCYTE ADHESION MOLECULE DURING ATHEROGENESIS [J].
CYBULSKY, MI ;
GIMBRONE, MA .
SCIENCE, 1991, 251 (4995) :788-791
[9]   Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice [J].
d'Uscio, LV ;
Baker, TA ;
Mantilla, CB ;
Smith, L ;
Weiler, D ;
Sieck, GC ;
Katusic, ZS .
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY, 2001, 21 (06) :1017-1022
[10]   Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products [J].
Dumitriu, IE ;
Baruah, P ;
Valentinis, B ;
Voll, RE ;
Herrmann, M ;
Nawroth, PP ;
Arnold, B ;
Bianchi, ME ;
Manfredi, AA ;
Rovere-Querini, P .
JOURNAL OF IMMUNOLOGY, 2005, 174 (12) :7506-7515