Abstract 528: Bone Marrow Angiotensin AT2 Receptor Deficiency Aggravates Atherosclerosis by Eliminating Macrophage Liver X Receptor-Mediated Antiatherogenic Actions

[BACKGROUND] The angiotensin II (Ang II) type 2 (AT2) receptor is crucially involved in atherogenesis; however, bone marrow (BM) AT2-mediated anti-atherogenic action remains undefined. [METHOD AND RESULT] We generated BM chimera apoE-deficient (apoE-/-) mice whose BM cells were repopulated with AT2-deficient (Agtr2-/-) or wild type (Agtr2+/+) cells. Eight weeks after BM transplantation, all mice were fed a western diet for two months. Atherosclerotic lesion area was significantly increased in apoE-/-/BM-Agtr2 -/- mice compared with apoE-/-/BM-Agtr2+/+ mice (51%, P -/- thioglycollate-induced peritoneal macrophages (TGPM) compared with Agtr2+/+ TGPM (P -/- TGPM (p -/- TGPM than Agtr2+/+ TGPM (34%, 53%, p -/- TGPM (24%, p [CONCLUSION] Our findings demonstrate that BM-AT2 deficiency aggravates atherosclerosis, at least in part, by eliminating anti-atherogenic properties elicited by macrophage LXR activation, suggesting that AT2-mediated regulation of macrophage LXR activity could be a novel therapeutic target for the prevention of atherosclerosis.