Efectes del tractament amb radioteràpia en pacients amb càncer de mama. Avaluació in vivo i in vitro de l’expressió dels miARNs-146a, -155, -221 i -222, i de la seva associació amb factors de risc cardiovasculars, resposta inflamatòria i disfunció endotelial

Identificador:  TDX:2877

Handle: https://hdl.handle.net/20.500.11797/TDX2877

Autors:  Esplugas Borràs, Roser

Resum:
Radiotherapy (RT) in breast cancer patients promotes the development of cardiovascular diseases (CVD-RT) as consequence of the radiation of heart and blood vessels. This CVD-RT derives from inflammatory response and endothelial dysfunction of vascular cells promoted by radiation. Currently, it was established that miRNAs-146a, -155, -221 and -222 are involved in these processes. Furthermore, miRNAs in blood has become attractive as biomarkers of diagnostic and progressive and as therapeutic agent of several diseases. In the present study, we evaluated the effects of RT on the expression of selected miRNAs in blood of women with breast cancer, and their potential as biomarkers in CVD-RT of these patients. In order to test if endothelial cells of blood vessels which were irradiated during RT are involved in the modulation of selected miRNAs levels, we studied the in vitro response to therapeutic dose of radiation in acute phase of the expression of these miRNAs on endothelial cells, as well as inflammatory response and endothelial dysfunction as possible mechanism of action. We observed an increase in the levels of selected miRNAs promoted by RT in blood of patients. Both miRNAs levels and RT-induced changes in their expression were associated with cardiovascular risk factors. Thus, we considered that these miRNAs could be used as CVD-RT biomarkers in these patients, despite further research is needed in order to validate their potential. Furthermore, we observed that radiation at therapeutic dose modulated the expression of selected miRNAs in endothelial cells in acute phase, but it did not promote inflammation or endothelial dysfunction as possible mechanism of action. Future studies should focus on the evaluation of these miRNAs levels as well as these CVD markers at further times, chronic exposition, to test if it exists a relationship.