Therapeutic potential of midkine in cardiovascular disease

Br J Pharmacol. 2014 Feb;171(4):936-44. doi: 10.1111/bph.12537.


Ischaemic heart disease, stroke and their pathological consequences are life-threatening conditions that account for about half of deaths in developed countries. Pathology of these diseases includes cell death due to ischaemia/reperfusion injury, vascular stenosis and cardiac remodelling. The growth factor midkine plays a pivotal role in these events. Midkine shows an acute cytoprotective effect in ischaemia/reperfusion injury at least in part via its anti-apoptotic effect. Moreover, while midkine promotes endothelial cell proliferation, it also recruits inflammatory cells to lesions. These activities eventually enhance angiogenesis, thereby preventing cardiac tissue remodelling. However, midkine's activity in recruiting inflammatory cells into the vascular wall also triggers neointima formation, and consequently, vascular stenosis. Moreover, midkine is induced in cancer tissues where it enhances angiogenesis. Therefore, midkine may promote tumour formation through its angiogenic and anti-apoptotic activity. This review focuses on the roles of midkine in ischaemic cardiovascular disease and their pathological consequences, that is angiogenesis, vascular stenosis, and cardiac remodelling, and discusses the possible therapeutic potential of modulation of midkine in these diseases.

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Keywords: angiogenesis; apoptosis; brain; cardioprotection; heart; infarction; inflammation; ischaemia/reperfusion; remodeling; vascular stenosis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism*
  • Cytokines / physiology*
  • Humans
  • Midkine
  • Neovascularization, Physiologic
  • Signal Transduction


  • Cytokines
  • Midkine