May 15, 2026Journal of the American College of Cardiology49 citations
FLT3 Activation Improves Post-Myocardial Infarction Remodeling Involving a Cytoprotective Effect on Cardiomyocytes
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Key Result
Intramyocardial injection of FLT3 ligand decreased infarct size and ameliorated post-myocardial infarction remodeling and function in mice by reducing apoptosis.
Key Points
- The study aims to investigate the role of FLT3 in cardiac remodeling after myocardial infarction.
- Induced myocardial infarction in mice using permanent ligation of the left anterior descending coronary artery.
- Administered intramyocardial injection of FLT3 ligand or vehicle into the infarct border zone.
- Assessed cardiac morphology and function via echocardiography and histology one week post-infarction.
- FLT3 ligand injection reduced infarct size and improved heart remodeling and function.
- Activation of FLT3 decreased myocardial apoptosis, particularly in the infarct border zone.
- FLT3 was upregulated under oxidative stress, suggesting cardiomyocytes are target cells, with protection provided via an Akt-dependent pathway.
Structured PICO
Does FLT3 activation via intramyocardial injection of FLT3 ligand improve post-myocardial infarction remodeling and function in mice?
P
Population
Mice with induced myocardial infarction via permanent ligation of the left anterior descending coronary artery, and in vitro cardiomyocytes
I
Intervention
Intramyocardial injection of FLT3 ligand (FL) into the infarct border zone
C
Comparator
Intramyocardial injection of vehicle
O
Outcome
Cardiac morphology and function assessed by echocardiography and histological analysis 1 week after infarctionsurrogate
FLT3 activation protects cardiomyocytes from oxidative stress-induced apoptosis and improves post-MI remodeling, highlighting its role as a cytoprotective system in the heart and a potential mechanism for TKI-induced cardiotoxicity.
Abstract
OBJECTIVES: The goal of this study was to define the role of FMS-like tyrosine kinase 3 (FLT3) in the heart. BACKGROUND: FLT3 is a prominent target of receptor tyrosine kinase inhibitors (TKIs) used for anticancer therapy. TKIs can cause cardiomyopathy but understanding of the mechanisms is incomplete, partly because the roles of specific TKI target receptors in the heart are still obscure. METHODS: Myocardial infarction was induced in mice by permanent ligation of the left anterior descending coronary artery followed by intramyocardial injection of FLT3 ligand (FL) or vehicle into the infarct border zone. Cardiac morphology and function were assessed by echocardiography and histological analysis 1 week after infarction. In addition, FLT3 expression and regulation, as well as molecular mechanisms of FLT3 action, were examined in cardiomyocytes in vitro. RESULTS: The intramyocardial injection of FL into the infarct border zone decreased infarct size and ameliorated post-myocardial infarction remodeling and function in mice. This beneficial effect was associated with reduced apoptosis, including myocytes in the infarct border zone. Cardiomyocytes expressed functional FLT3, and FLT3 messenger ribonucleic acid and protein were up-regulated under oxidative stress, identifying cardiomyocytes as FL target cells. FLT3 activation with FL protected cardiomyocytes from oxidative stress-induced apoptosis via an Akt-dependent mechanism involving Bcl-2 family protein regulation and inhibition of the mitochondrial death pathway. CONCLUSIONS: FLT3 is a cytoprotective system in the heart and a potential therapeutic target in ischemic cardiac injury. The protective mechanisms uncovered here may be further explored in view of potential cardiotoxic effects of FLT3-targeting anticancer therapy, particularly in patients with ischemic heart disease.