Exosomal microRNAs as circulating biomarkers and mediators of the cardioprotective effect in patients undergoing cancer therapies

Abstract

Cancer and cardiovascular (CV) disease are a significant global public health issue and remain the main causes of morbidity and mortality worldwide. Anti-cancer therapy based on cardiotoxic agents such as the anthracyclines (DNA intercalating Topoisomerase II inhibitors) can lead to irreversible damage on cardiomyocytes ultimately causing heart failure. Strong efforts have been made to detect the diseases at early stages as well as to enhance regimens to develop new therapies. In this context, microRNAs (miRNAs) are emerging as new therapy and biomarkers to various diseases. It has been demonstrated that miRNAs are protected from degradation on the body fluids packaged into microparticles, as exosomes. This study aims detect miRNAs candidates as non-invasive biomarkers of cardiotoxicity induced by chemotherapy. In addition to chemotherapy, aerobic exercise training (AET) have been efficiently supporting the treatment of cardiovascular diseases and different types of cancer, however, little is known about the mechanisms behind exercise-mediated protection. Thus, the aims of the project are the following: 1) To use cell and animal models to investigate the functional role of miRNAs in cardiotoxicity due to chemotherapy; 2) To investigate the potential of exosomal miRs as new circulating biomarkers of cardiac changes in cancer-bearing subjects receiving chemotherapy. (AU)