The Flt3-inhibitor quizartinib augments apoptosis and promotes maladaptive remodeling after myocardial infarction in mice.

ABSTRACT:

Background

Tyrosine kinase inhibitors (TKIs) targeting fms-like tyrosine kinase 3 (Flt3) such as quizartinib were specifically designed for acute myeloid leukemia treatment, but also multi-targeting TKIs applied to solid tumor patients inhibit Flt3. Flt3 is expressed in the heart and its activation is cytoprotective in myocardial infarction (MI) in mice.

Objectives

We sought to test whether Flt3-targeting TKI treatment aggravates cardiac injury after MI.

Methods and results

Compared to vehicle, quizartinib (10 mg/kg/day, gavage) did not alter cardiac dimensions or function in healthy mice after four weeks of therapy. Pretreated mice were randomly assigned to MI or sham surgery while receiving quizartinib or vehicle for one more week. Quizartinib did not aggravate the

SUBMITTER: Monogiou Belik D 

PROVIDER: S-EPMC10873224 | biostudies-literature | 2024 Apr

REPOSITORIES: biostudies-literature