Lack 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 release secretory vesicles called granules, and certain granule proteins, such as CRAMP (or LL37 in humans), are able to recruit other inflammatory cell types. To determine whether this happens during atherosclerotic lesion formation, Döring et al examined atherosclerosis-prone mice lacking CRAMP. Sure enough, these mice had fewer inflammatory cells adhering to their blood vessel walls, which resulted in smaller atherosclerotic plaques containing a reduced proportion of macrophages. CRAMP previously has been detected in endothelial cells and macrophages, but the team showed that in atherosclerotic vessels, CRAMP was specifically upregulated in neutrophils. The team also found that CRAMP promotes inflammatory cell recruitment by interacting with their formyl-peptide membrane receptors. Blocking these receptors, or indeed CRAMP activity, may be an avenue toward atherosclerosis therapies, as suggested by the authors. Sensing Gene-Regulatory Hyperglycemic Changes by Set7 in Vascular Endothelial Cells (p 1067)