Protease-activated receptor 1 activation enhances doxorubicin-induced cardiotoxicity.

ABSTRACT:

Objective

The anti-cancer anthracycline drug Doxorubicin (Dox) causes cardiotoxicity. We investigated the role of protease-activated receptor 1 (PAR-1) in Dox-induced cardiotoxicity.

Methods and results

In vitro experiments revealed that PAR-1 enhanced Dox-induced mitochondrial dysfunction, reactive oxygen species and cell death of cardiac myocytes and cardiac fibroblasts. The contribution of PAR-1 to Dox-induced cardiotoxicity was investigated by subjecting PAR-1^-/- mice and PAR-1^+/+ mice to acute and chronic exposure to Dox. Heart function was measured by echocardiography. PAR-1^-/- mice exhibited significant less cardiac injury and dysfunction compared to PAR-1^+/+ mice after acute and chronic Dox administration. PAR-1^-/-

SUBMITTER: Antoniak S 

PROVIDER: S-EPMC6173317 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature