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Doxorubicin-induced cardiotoxicity is mediated by neutrophils through release of neutrophil elastase.
Bhagat, Anchit; Shrestha, Pradeep; Jeyabal, Prince; Peng, Zhanglong; Watowich, Stephanie S; Kleinerman, Eugenie S.
Affiliation
  • Bhagat A; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
  • Shrestha P; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
  • Jeyabal P; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
  • Peng Z; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
  • Watowich SS; Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
  • Kleinerman ES; Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Front Oncol ; 12: 947604, 2022.
Article in En | MEDLINE | ID: mdl-36033503
The mechanisms by which Doxorubicin (Dox) causes acute and late cardiotoxicity are not completely understood. One understudied area is the innate immune response, and in particular the role of neutrophils in Dox-induced cardiotoxicity. Here, using echocardiography, flow cytometry and immunofluorescence staining, we demonstrated increased infiltration of neutrophils that correlated with decreased heart function, disruption of vascular structures and increased collagen deposition in the heart after Dox treatment. Depleting neutrophils protected the heart from Dox-induced cardiotoxicity and changes in vascular structure. Furthermore, our data using neutrophil elastase (NE) knock-out mice and the NE inhibitor AZD9668 suggest that neutrophils cause this damage by releasing NE and that inhibiting NE can prevent Dox-induced cardiotoxicity. This work shows the role of neutrophils and NE in Doxorubicin-induced cardiotoxicity for the first time and suggests a new possible therapeutic intervention.
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Oncol Year: 2022 Document type: Article Affiliation country: Estados Unidos Country of publication: Suiza

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Front Oncol Year: 2022 Document type: Article Affiliation country: Estados Unidos Country of publication: Suiza