RATIONALE: Neutrophils have been reported to contribute to early atherosclerotic lesion formation. Mechanisms of neutrophil-driven atherosclerosis remain unclear so far. OBJECTIVE: Investigation of the role of the neutrophil granule protein cathelicidin (CRAMP in mouse, LL37 in human) in atherosclerosis. METHODS AND RESULTS: Compared to Apoe(-/-) mice, Cramp(-/-) Apoe(-/-) mice exhibit reduced lesion sizes with lower macrophage numbers. In atherosclerotic aortas, we could detect CRAMP specifically in neutrophils, but not in monocytes or macrophages. By use of intravital microscopy, CRAMP was found to be deposited by activated neutrophils on inflamed endothelium of large arteries. In this location cathelicidins promote adhesion of classical monocytes and neutrophils, but not nonclassical monocytes in a formyl-peptide receptor-dependent manner. CONCLUSIONS: Cathelicidins promote atherosclerosis by enhancement of the recruitment of inflammatory monocytes.
RATIONALE: Neutrophils have been reported to contribute to early atherosclerotic lesion formation. Mechanisms of neutrophil-driven atherosclerosis remain unclear so far. OBJECTIVE: Investigation of the role of the neutrophil granule protein cathelicidin (CRAMP in mouse, LL37 in human) in atherosclerosis. METHODS AND RESULTS: Compared to Apoe(-/-) mice, Cramp(-/-) Apoe(-/-) mice exhibit reduced lesion sizes with lower macrophage numbers. In atherosclerotic aortas, we could detect CRAMP specifically in neutrophils, but not in monocytes or macrophages. By use of intravital microscopy, CRAMP was found to be deposited by activated neutrophils on inflamed endothelium of large arteries. In this location cathelicidins promote adhesion of classical monocytes and neutrophils, but not nonclassical monocytes in a formyl-peptide receptor-dependent manner. CONCLUSIONS: Cathelicidins promote atherosclerosis by enhancement of the recruitment of inflammatory monocytes.
Authors: Almudena Ortega-Gomez; Melanie Salvermoser; Jan Rossaint; Robert Pick; Janine Brauner; Patricia Lemnitzer; Jessica Tilgner; Renske J de Jong; Remco T A Megens; Janina Jamasbi; Yvonne Döring; Christine T Pham; Christoph Scheiermann; Wolfgang Siess; Maik Drechsler; Christian Weber; Jochen Grommes; Alexander Zarbock; Barbara Walzog; Oliver Soehnlein Journal: Circulation Date: 2016-09-22 Impact factor: 29.690