Project R-11235

From Onco to Cardio: AGEs as a new target for chemotherapyinduced cardiotoxicity. (Research)

The cancer patients of today are the cardiac patients of tomorrow. Chemotherapy is lifesaving but induces cardiac dysfunction. Doxorubicin is an effective chemotherapeutic agent but is toxic to the heart. The chance of getting heart failure after doxorubicin treatment depends on the dosage, rising to 48% at a high dose. Increased oxidative stress is thought to be the major culprit. However, many aspects of the underlying mechanisms remain unknown and effective cardioprotection is lacking. This leads to inadequate care of this specific patient population. Growing evidence illustrates that glycated proteins (i.e. AGEs) accumulate in patients with cardiac dysfunction. In addition, I recently found increased AGEs levels in the blood and the presence of AGEs in the hearts of rats treated with doxorubicin. In my project proposal, I hypothesize that AGEs impair the function and structure of cardiac muscle cells after doxorubicin chemotherapy, resulting in global cardiac dysfunction. First, I investigate the deleterious effects of AGEs. Second, I inhibit the formation of AGEs to prevent cardiac dysfunction. In the long term, AGEs might become novel targets to offer cardioprotection in cancer patients receiving doxorubicin chemotherapy.

01 November 2020 - 31 October 2022