Apoptosis induction of cardiomyocytes and subsequent fibrosis after irradiation and neoadjuvant chemotherapy.
OBJECTIVE
Breast cancer treatments can induce important cardiovascular complications. The aim of this study was to evaluate cardiac alterations after irradiation and chemotherapy in an animal model.


METHODS
Wistar rats were divided into three groups: Control, TC+ IR (received chemotherapy and irradiation) and IR (received only irradiation). After 5 months, echocardiography was performed, the animals were euthanized, and the left ventricle was analyzed using light microscopy techniques and Polymerase Chain Reaction (PCR).


RESULTS
Echocardiography showed decreases in ejection fraction and cardiac output, in TC+ IR group. Both TC+ IR and IR showed reduced intramyocardial vessel-to-cardiomyocyte ratio, increased connective tissue, cardiomyocyte hypertrophy, increased numbers of apoptotic nuclei and increased Bax/Bcl2 expression. We also observed increased Transforming growth factor (TGF) beta 1 mRNA expression in both groups, but type 1 Procollagen expression was increased in TC+ IR group only.


CONCLUSIONS
The study suggests that the induced cardiac remodelling begins with the reduction of intramyocardial vessels in the left ventricle tissue. The main consequence is the loss of cardiomyocytes through apoptosis, leading to the replacement of healthy tissue by fibrous tissue. It was observed that the damage caused by the combination of irradiation and chemotherapy induced functional alterations that did not occur when the animals were only irradiated.
Laboratório de Ciências Radiológicas, Departamento de Biofísica e Biometria.
Camila
C
Salata
Samara Cristina
SC
Ferreira-Machado
Cherley Borba Vieira
CB
De Andrade
André Luiz
AL
Mencalha
Carlos Alberto
CA
Mandarim-De-Lacerda
Carlos Eduardo
CE
de Almeida
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D004452:Echocardiography; D005260:Female; D005355:Fibrosis; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects*; D020360:Neoadjuvant Therapy; D051381:Rats; D017208:Rats, Wistar; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D016277:Ventricular Function, Left / Q000187:drug effects / Q000528:radiation effects
D053773:Transforming Growth Factor beta1