Key result
BMP10 overexpression or supplementation alleviated doxorubicin-induced oxidative stress, apoptosis, and cardiac dysfunction in a STAT3-dependent manner.
Why the study?
Doxorubicin causes life-threatening cardiac injury, but the role of bone morphogenetic protein 10 (BMP10) in this injury has not been explored.
Does BMP10 overexpression or supplementation alleviate doxorubicin-induced cardiac injury in mice?
Does BMP10 overexpression or supplementation alleviate doxorubicin-induced cardiac injury in mice?
BMP10 protects against doxorubicin-induced cardiac injury by activating the STAT3 signaling pathway, highlighting its potential as a therapeutic agent for DOX-induced cardiotoxicity.
Suggests a novel cardioprotective pathway against anthracycline toxicity; leaves open.
Doxorubicin (DOX) has limited antitumor applications owing to its association with life-threatening cardiac injury. Oxidative damage and cardiac apoptosis are crucial in DOX-induced cardiac injury. Bone morphogenetic protein 10 (BMP10) is predominantly distributed in the heart and acts as a cardioprotective factor that preserves cardiac function. However, the role of BMP10 in DOX-induced cardiac injury has not yet been explored. The current study aimed to examine the function and mechanism of action of BMP10 in DOX-induced cardiac injury. An adeno-associated viral system was used for the overexpression or silencing of cardiac-specific BMP10, and subsequently, a single dose of DOX was intraperitoneally injected to induce cardiac injury. Results showed that DOX exposure decreased BMP10 expression in the heart. Cardiac-specific overexpression of BMP10 alleviated the oxidative stress and apoptosis and improved cardiac function. Conversely, cardiac-specific silencing of BMP10 aggravated the redox disorder and apoptosis and worsened the cardiac dysfunction caused by DOX. Exogenous BMP10 supplementation amelioratesd the DOX-induced cardiac contractile dysfunction. Mechanistically, we found that phosphorylation of signal transducer and activator of transcription 3 (STAT3) is reduced in DOX-induced cardiotoxicity, and, BMP10 activated impaired STAT3 via a non-canonical pathway. BMP10 lost its cardioprotective function in cardiomyocyte-specific STAT3 knockout (STAT3-cKO) mice. Based on our findings, we suggested that BMP10 is a potential therapeutic agent against DOX-induced cardiac injury and that the cardioprotective effects of BMP10 are dependent on the activation of STAT3.
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An et al. (2022) studied Doxorubicin-induced cardiac injury. Bone morphogenetic protein 10 (BMP10) overexpression or supplementation vs. DOX alone or BMP10 silencing was evaluated on Cardiac function, oxidative stress, and apoptosis. BMP10 overexpression or supplementation alleviated doxorubicin-induced oxidative stress, apoptosis, and cardiac dysfunction in a STAT3-dependent manner.
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