Midkine is a multifunctional growth factor, and its serum levels are increased with the functional severity of heart failure. This study aimed to examine the role of midkine in heart failure pathogenesis. Midkine expression levels were increased in the kidney and lung after transverse aortic constriction (TAC) surgery, but not sufficiently increased in the heart. After TAC, phosphorylation of extracellular signal-regulated kinase1/2 and AKT, and the expression levels of foetal genes in the heart were considerably increased in transgenic mice with cardiac-specific overexpression of midkine (MK-Tg) compared with wild-type (WT) mice. MK-Tg mice showed more severe cardiac hypertrophy and dysfunction, and showed lower survival rate after TAC than WT mice. We conclude that midkine plays a critical role in cardiac hypertrophy and remodelling. (C) 2013 The Authors. Published by Elsevier Inc. All rights reserved.