The Cardiotoxicology of Anthracycline Chemotherapeutics: TRANSLATING MOLECULAR MECHANISM INTO PREVENTATIVE MEDICINE

Paracrine signaling between cardiac endothelial cells and ventricular myocytes. A. As illustrated in this section of rat myocardium, ventricular myocytes are surrounded by microvascular endothelial capillaries. Besides supplying blood flow per se, the microvascular endothelial cells provide trophic support to the myocytes, which modulates cardiac structure and function. B. Beyond its role as a “glial growth factor,” neuregulin acts also as a paracrine signal between cardiac microvascular endothelial cells and ventricular myocytes. Neuregulin is expressed in the microvascular endothelial cell and protects myocytes from injury in the presence of anthracyclines and other cell stresses. Neuregulin activates erbB2 and erbB4 receptor tyrosine kinases in myocytes, thus regulating several downstream signaling cascades.