Crosstalk of lipids and inflammation in atherosclerosis: the PRO of PGRN?

This editorial refers to ‘Deletion of progranulin exacerbates atherosclerosis in ApoE knockout mice’ by R. Kawase et al ., doi:10.1093/cvr/cvt178. Atherosclerosis is recognized as a chronic inflammatory process that accelerates in the context of high cholesterol levels.1 The unique aspect of atherosclerosis, over other inflammatory diseases, is the major effect of the cholesterol environment. There is accumulating evidence that lipids can influence inflammatory responses and vice versa, but so far the lipid and inflammatory components that initiate atherosclerotic disease have mainly been studied as two separate pathogenic entities. Elucidation of the functional denominators that link immune activation and derailed cholesterol metabolism may facilitate the development of novel therapeutic strategies to treat atherosclerosis. Evidence is accumulating that supports the relevance of cross-talk of lipid metabolism and the immune responses in vascular pathology. For instance lipid loading induces a distinct, unique gene expression profile in macrophages within the atherosclerotic lesion.2 It also was shown that cholesterol crystals (consequence of extreme cholesterol loading) that are present in early atherosclerotic lesions, can induce inflammasome activation and may thus be considered as a novel initiators of inflammation.3,4 In this issue of cardiovascular research, Kawase et al .5 describe a role for the growth factor progranulin (PGRN) in the pathogenesis of atherosclerosis. Data are presented suggesting that PGRN is a glycoprotein that strongly influences and inhibits detrimental immune responses. PGRN is a protein that may exert a role in the cross-talk of immunity and lipid turnover, as it has both …