Increased expression of the TGF-b superfamily cytokine MIC-1/GDF15 protects ApoE-/- mice from the development of atherosclerosis

Aim: MIC-1/GDF15 is a member of the TGF-b superfamily, which is thought to have pleiotropic roles in stress responses, inflammation, tissue injury and repair, energy homeostasis, and malignancy. MIC-1/GDF15 was recently identified as a new biomarker for the development of cardiovascular events and the outcome of atherosclerotic disease therapy. The aim of our study was to determine if MIC-1 also directly exerts pro- or antiatherogenic properties during the development of atherosclerosis. Methods and results: We investigated the effect of transgenic overexpression of MIC-I in macrophages in the ApoE(-/-) mouse model of atherosclerosis. After 6 months of high-fat diet, MIC-1/GDF 15 transgenic ApoE(-/-) mice had smaller atherosclerotic lesions; however, no differences in lesion composition, pro- or anti-inflammatory cytokine production, or serum levels of lipids or cytokines were detected. Conclusions: Our results suggest that MIC-1 has an overall protective effect on the disease process, but further studies will be required to define its mechanism of action. (C) 2012 Elsevier Inc. All rights reserved.