Functions for the cardiomyokine, MANF, in cardioprotection, hypertrophy and heart failure

J Mol Cell Cardiol. 2011 Oct;51(4):512-7. doi: 10.1016/j.yjmcc.2010.10.008. Epub 2010 Oct 21.


We define cardiomyokines as heart-derived secreted proteins that affect cardiovascular function via autocrine, paracrine and/or endocrine mechanisms. The subject of this review is the cardiomyokine, mesencephalic astrocyte-derived neurotrophic factor (MANF). The expression of MANF is increased in the ischemic heart, in part, through activation of ER stress, a condition that drastically impairs the expression and secretion of most cardiomyokines. This novel function of MANF suggests that it may have important roles in the ER stressed, ischemic heart. Consistent with this are recent findings showing that MANF protects against ischemic damage, and that it is anti-hypertrophic. Accordingly, in light of its function as a potentially secreted cardiomyokine, MANF has translational potential as a novel therapy for ischemic heart disease. This article is part of a special issue entitled "Key Signaling Molecules in Hypertrophy and Heart Failure."

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cardiomegaly / drug therapy
  • Cardiomegaly / physiopathology*
  • Endoplasmic Reticulum Stress
  • Gene Expression
  • Heart Failure / drug therapy
  • Heart Failure / physiopathology*
  • Humans
  • Molecular Sequence Data
  • Molecular Targeted Therapy
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Nerve Growth Factors / physiology*
  • Translational Research, Biomedical


  • MANF protein, human
  • Nerve Growth Factors