Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity

Area of Science:

• Cardio-oncology
• Metabolomics
• Biochemistry

Background:

• Tyrosine kinase inhibitors (TKIs) are vital cancer treatments but cause cardiovascular toxicity.
• Metabolomics offers a way to detect early biochemical changes and guide interventions.

Purpose of the Study:

• To synthesize metabolomic, proteomic, and transcriptomic data on TKI cardiotoxicity.
• To identify mechanistic themes and propose metabolomics-guided interventions.

Main Methods:

• Narrative synthesis of preclinical and translational studies.
• Focus on untargeted and targeted metabolomic findings.
• Functional validation in rodent and cellular models.

Main Results:

• Convergent metabolomic signatures of TKI cardiotoxicity identified: mitochondrial dysfunction, disrupted nitric oxide signaling, and inflammation.
• Rodent models confirmed these signatures and showed histological/functional injury.
• L-carnitine intervention restored myocardial function and fatty acid oxidation.

Conclusions:

• Metabolomics can identify biomarkers for early detection and prevention of TKI cardiotoxicity.
• Metabolomics-guided cardioprotection is feasible.
• Prospective validation is needed for precision cardio-oncology.