UltraRapid Communication Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice
نویسندگان
چکیده
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. (Circ Res. 2012;110:00-00.)
منابع مشابه
Brief UltraRapid Communication Lack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice
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 si...
متن کاملLack of neutrophil-derived CRAMP reduces atherosclerosis in mice.
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...
متن کاملLack of Neutrophil-Derived CRAMP Reduces Atherosclerosis in Mice (p 1052)
Döring et al reveal how neutrophils promote atherosclerosis, and suggest a way to stop it. Atherosclerosis is a chronic inflammatory disorder associated with lipid accumulation in the vessel wall. Although the inflammation is known to be promoted, at least in part, by neutrophils, the precise mechanism by which these cells contribute to atherogenesis remains unclear. When activated, neutrophils...
متن کاملThe cathelicidin protein CRAMP is a potential atherosclerosis self-antigen in ApoE(-/-) mice
Auto-immunity is believed to contribute to inflammation in atherosclerosis. The antimicrobial peptide LL-37, a fragment of the cathelicidin protein precursor hCAP18, was previously identified as an autoantigen in psoriasis. Given the reported link between psoriasis and coronary artery disease, the biological relevance of the autoantigen to atherosclerosis was tested in vitro using a truncated (...
متن کاملNeutrophils in Atherosclerosis
Inflammation and activation of immune cells are key mechanisms in the development of atherosclerosis.1 Elegant experimental studies, typically performed in compound mutant mice susceptible to diet-induced atherosclerosis, indicate important roles for monocytes, T lymphocytes, and mast cells in lesion formation (Figure). Moreover, inflammatory pathways promote thrombosis, a late complication of ...
متن کامل