| First Author | Tang EH | Year | 2011 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 31 |
| Issue | 2 | Pages | 261-9 |
| PubMed ID | 21088251 | Mgi Jnum | J:184180 |
| Mgi Id | MGI:5320392 | Doi | 10.1161/ATVBAHA.110.216580 |
| Citation | Tang EH, et al. (2011) Deletion of EP4 on bone marrow-derived cells enhances inflammation and angiotensin II-induced abdominal aortic aneurysm formation. Arterioscler Thromb Vasc Biol 31(2):261-9 |
| abstractText | OBJECTIVE: To examine whether a lack of prostaglandin E receptor 4 (EP4) on bone marrow-derived cells would increase local inflammation and enhance the formation of abdominal aortic aneurysm (AAA) in vivo. METHODS AND RESULTS: Prostaglandin E(2) (PGE(2)) through activation of EP4, can mute inflammation. Hypercholesterolemic low-density lipoprotein receptor knockout (LDLR(-/-)) mice transplanted with either EP4(+/+) (EP4(+/+)/LDLR(-/-)) or EP4(-/-) (EP4(-/-)/LDLR(-/-)) bone marrow received infusions of angiotensin II to induce AAA. Deficiency of EP4 on bone marrow-derived cells increased the incidence (50% of male EP4(+/+)/LDLR(-/-) mice versus 88.9% of male EP4(-/-)/LDLR(-/-) mice developed AAA; and 22% of female EP4(+/+)/LDLR(-/-) mice versus 83.3% of female EP4(-/-)/LDLR(-/-) mice developed AAA) and severity of AAA, increased monocyte chemoattractant protein-1 (2.72-fold in males and 1.64-fold in females), and enhanced infiltration of macrophages (3.8-fold in males and 2.44-fold in females) and T cells (1.88-fold in males and 1.66-fold in females) into AAA lesions. Lack of EP4 on bone marrow-derived cells augmented elastin fragmentation, increased apoptotic markers, and decreased smooth muscle cell accumulation within AAA lesions. CONCLUSIONS: Deficiency of EP4 on bone marrow-derived cells boosted inflammation and AAA formation induced by angiotensin II in hyperlipidemic mice. This study affirms the pathophysiologic importance of PGE(2) signaling through EP4 as an endogenous anti-inflammatory pathway involved in experimental aneurysm formation. |
