Therapeutic Potential of Midkine in Cardiovascular Diseases

Abstract

Ischemic heart disease, stroke and their pathological consequences are life-threatening diseases that account for about half of deaths in developed countries. Pathology of these diseases includes cell death due to ischemia/reperfusion injury, vascular stenosis, and cardiac remodeling. The growth factor midkine plays a pivotal role in these events. Midkine shows an acute cytoprotective effect in ischemia/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 remodeling. 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 tumor formation through its angiogenic and anti-apoptotic activity. This review focuses on the roles of midkine in ischemic cardiovascular diseases and their pathological consequences, i.e. angiogenesis, vascular stenosis, and cardiac remodeling, and discusses the possible therapeutic potential of modulation of midkine in these diseases.