RNLS and Interstitial cardiac fibrosis: Additional findings relevant to this review indicate that renalase supplementation prevents deterioration of cardiac function and structure in terms of a lower degree of cardiomyocyte hypertrophy, ameliorated cardiac interstitial fibrosis (cardiac upregulation of matrix metalloproteinase (MMP)-1, down-regulation of tissue inhibitor of metalloproteinase (TIMP)-1 and TGF-β1, and silencing of ERK1/2 phosphorylation), decreased left ventricular (LV) end-diastolic posterior wall thickness, and LV end-diastolic pressure as well as a restored cardiac diastolic function [114].