Open AccessMMP inhibitors attenuate doxorubicin cardiotoxicity by preventing intracellular and extracellular matrix remodelling
Author(s) -
Brandon Chan,
Andrej Roczkowsky,
Woo Jung Cho,
Mathieu Poirier,
Consolato Sergi,
Vic Keschrumrus,
Jared M. Churko,
Henk Granzier,
Richard Schulz
Publication year - 2020
Publication title -
cardiovascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.774
H-Index - 219
eISSN - 1755-3245
pISSN - 0008-6363
DOI - 10.1093/cvr/cvaa017
Subject(s) - cardiotoxicity , doxorubicin , heart failure , myofilament , matrix metalloproteinase , medicine , chemistry , pharmacology , chemotherapy , myocyte
Heart failure is a major complication in cancer treatment due to the cardiotoxic effects of anticancer drugs, especially from the anthracyclines such as doxorubicin (DXR). DXR enhances oxidative stress and stimulates matrix metalloproteinase-2 (MMP-2) in cardiomyocytes. We investigated whether MMP inhibitors protect against DXR cardiotoxicity given the role of MMP-2 in proteolyzing sarcomeric proteins in the heart and remodelling the extracellular matrix.