Key result
Cardiac-specific ANGPTL2 overexpression exacerbated doxorubicin-induced cardiac dysfunction, myocardial apoptosis, and oxidative stress by inhibiting the DUSP1 pathway in mice.
Why the study?
The connection of angiopoietin-like protein 2 (ANGPTL2) to doxorubicin-related cardiomyopathy remains elusive.
Does ANGPTL2 modulation affect doxorubicin-induced cardiotoxicity in a murine model?
Does ANGPTL2 modulation affect doxorubicin-induced cardiotoxicity in a murine model?
ANGPTL2 aggravates doxorubicin-induced cardiotoxicity by suppressing the DUSP1 pathway, suggesting a potential therapeutic target for DOX-related cardiomyopathy.
ANGPTL2 overexpression worsened DOX cardiotoxicity in mice via DUSP1; hypothesis-generating for targeted cardioprotection in patients.
Angiopoietin-like protein 2 (ANGPTL2) plays versatile roles in various cardiovascular diseases. Its connection to doxorubicin (DOX)-related cardiomyopathy, however, remains elusive. To determine the role of ANGPTL2, an adeno-associated viral vector was used to overexpress ANGPTL2 in the murine heart 4 weeks before DOX treatment (15 mg/kg). Moreover, mice were injected with adenoviral vectors to knock down ANGPTL2 in the myocardium. Echocardiography and hemodynamics were used to determine the cardiac function. The effect of ANGPTL2 and its downstream target were elucidated by applying molecular and biochemical strategies. We found that ANGPTL2 expression was significantly increased in response to DOX stimulation. Moreover, cardiac-specific ANGPTL2 overexpression exacerbated DOX-related cardiac dysfunction, myocardial apoptosis, and oxidative stress. Mechanistically, ANGPTL2 aggravated DOX-induced cardiac injury via inhibiting the dual specificity phosphatase 1 (DUSP1) pathway and DUSP1 overexpression significantly impeded DOX-induced cardiomyopathy in ANGPTL2-overexpressed mice. Altogether, ANGPTL2 aggravated DOX-related cardiac injury by suppressing the DUSP1 pathway.
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Liu et al. (2022) studied Doxorubicin-induced cardiomyopathy. ANGPTL2 overexpression or knockdown was evaluated on Cardiac dysfunction, myocardial apoptosis, and oxidative stress. Cardiac-specific ANGPTL2 overexpression exacerbated doxorubicin-induced cardiac dysfunction, myocardial apoptosis, and oxidative stress by inhibiting the DUSP1 pathway in mice.
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