In contrast to the hypothesis of the potential anti-inflammatory behavior of sTWEAK, animal studies with different approaches to investigate the role of TWEAK/Fn14 axis in the development and progression of atherosclerosis, gain of function, or loss of function, have showed that TWEAK participates in the atherogenic process (63, 64) indicating that the “net” effect of the pathway is damaging rather than protective in this condition. This evidence concerns the gene TNFSF12 and atherosclerosis.