ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway

Liu, Cheng1,2,3; Chen, Qiuling2,4; Liu, Huadong1,2,3

2022-09-01

10.1093/bbb/zbac156

BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY   Impact Factor & Quartile

0916-8451

1347-6947

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.

cardiomyopathy oxidative stress doxorubicin ANGPTL2 DUSP1

SCI

English

Corresponding

Shenzhen Science and Technology Project[JCYJ20190806153207263] ; Shenzhen Key Medical Discipline Construction Fund["SZXK059","SZXK003"]

Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Chemistry ; Food Science & Technology

Biochemistry & Molecular Biology ; Biotechnology & Applied Microbiology ; Chemistry, Applied ; Food Science & Technology

WOS:000864369900001

OXFORD UNIV PRESS

BIOLOGY & BIOCHEMISTRY

Web of Science

1.Jinan Univ, Clin Med Coll 2, Dept Cardiol, Shenzhen Peoples Hosp, Shenzhen, Peoples R China
2.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen, Peoples R China
3.Shenzhen Cardiovasc Minimally Invas Med Engn Tech, Shenzhen, Peoples R China
4.Jinan Univ, Dept Pharm, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen, Peoples R China

Liu, Cheng,Chen, Qiuling,Liu, Huadong. ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway[J]. BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY,2022.

Liu, Cheng,Chen, Qiuling,&Liu, Huadong.(2022).ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway.BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY.

Liu, Cheng,et al."ANGPTL2 aggravates doxorubicin-induced cardiotoxicity via inhibiting DUSP1 pathway".BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY (2022).