Endoglin has been identified to play a functional role as a regulator of TGFβ1 signaling, particular in TGFβ1-mediated calcineurin expression. The present invention features methods of reducing cardiac damage, particularly in a subject undergoing chemotherapy or radiation therapy by administering a composition that inhibits endoglin activity. The present invention also features methods of treating autoimmune diseases, inflammatory diseases, organ transplantation, and conditions association with oxidative stress related to TGFβ1-mediated calcineurin expression and reactive oxygen species (ROS) production by administering a composition that inhibits endoglin activity. The present invention also features methods of treating fibrotic diseases by administering a composition that inhibits endoglin activity.