Dickkopf-3: a stubborn protector of cardiac hypertrophy

Abstract

This editorial refers to ‘Dickkopf-3 attenuates pressure overload-induced cardiac remodelling’ by Y. Zhang et al. , pp. 35–45, this issue. In response to haemodynamic overload under pathological conditions such as hypertension, valvular heart disease, and myocardial infarction, the heart undergoes hypertrophic growth by increasing cell size and protein synthesis as well as changing the transcriptional programme in cardiac myocytes.1 Although cardiac hypertrophy is beneficial in the way that it reduces ventricular wall tension and maintains pump function, it promotes cardiac structural remodelling and dysfunction, and eventually leads to development of congestive heart failure, arrhythmia, and sudden death. At present, several drugs such as inhibitors of the renin–angiotensin–aldosterone system, β-adrenergic receptor blockers, and calcium channel blockers are clinically available for the management of hypertension, and these drugs have shown significant efficacy in preventing load-induced cardiac hypertrophy and remodelling. However, these pharmacological agents are currently of limited effectiveness, and further discovery and development of novel classes of cardioprotective drugs are in urgent need.2 For that purpose, it is important to elucidate the molecular mechanisms underlying the development of cardiac hypertrophy. In the article by Zhang et al. ,3 integrating genetic approaches in mice have shed light on Dickkopf-3 (DKK3) as a cardioprotective regulator of cardiac hypertrophy. DKK3 is a secreted glycoprotein of the Dickkopf family that typically antagonizes the Wnt/β-catenin signalling by interfering with Wnt co-receptors, low-density lipoprotein receptor-related protein and kremen.4 ‘Dickkopf’ is a German word for ‘big head’ or ‘stubborn’, and the protein …