However in vivo, these cardioprotective effects of RKIP seem to be linked to a defective Nnt locus, because in the presence of an intact Nnt locus and unrestrained mitochondrial ROS generation under cardiac stress such as pressure overload, endogenously expressed RKIP levels are sufficient to promote detrimental cardiac effects such as myocardial fibrosis [23,140]. This evidence concerns the gene NNT and Myocardial fibrosis.