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

Evis Harja, De Xiu Bu, Barry I. Hudson, Sun Chang Jong, Xiaoping Shen, Kellie Hallam, Anastasia Z. Kalea, Yan Lu, Rosa H. Rosario, Sai Oruganti, Zana Nikolla, Dmitri Belov, Evanthia Lalla, Ravichandran Ramasamy, Fang Yan Shi, Ann Marie Schmidt

Research output: Contribution to journalArticlepeer-review

280 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)183-194
Number of pages12
JournalJournal of Clinical Investigation
Issue number1
StatePublished - Jan 2 2008
Externally publishedYes

ASJC Scopus subject areas

  • Medicine(all)


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