Growth differentiation factor 15 deficiency protects against atherosclerosis by attenuating CCR2-mediated macrophage chemotaxis

• DOI: 10.1084/jem.20100370
• Publication Date: 2011-01-18T03:59:15Z
• Authors: Saskia C.A. de Jager; Beatriz Bermúdez; Ilze Bot; Rory R. Koenen; Martine Bot; Annemieke Kavelaars; Vivian de Waard; Cobi J. Heijnen; Francisco J.G. Mu...; Christian Weber; Theo J.C. van Berkel; Johan Kuiper; Se-Jin Lee; Rocio Abia; Erik A.L. Biessen
• Keywords: CCR2; GDF15

Growth differentiation factor (GDF) 15 is a member of the transforming growth β (TGF-β) superfamily, which operates in acute phase responses through currently unknown receptor. Elevated GDF-15 serum levels were recently identified as risk for coronary syndromes. We show that expression up-regulated disease progresses murine atherosclerosis and primarily colocalizes with plaque macrophages. Hematopoietic deficiency low density lipoprotein receptor−/− mice led to impaired initial lesion formation increased collagen later lesions. Although burden GDF-15−/− chimeras was unaltered, plaques had reduced macrophage infiltrates decreased necrotic core formation, all features improved stability. In vitro studies pointed TGFβRII-dependent regulatory role cell death regulation. Importantly, macrophages displayed CCR2 expression, whereas promoted chemotaxis strictly CCR2- manner, phenomenon not observed G protein–coupled receptor kinase 2+/− conclusion, deletion has beneficial effect both early by inhibition CCR2-mediated modulating death. Our study first identify an modifier CCR2/TGFβRII-dependent inflammatory vascular injury.