Apelin, Cortisol, and Doxorubicin-Induced Cardiotoxicity: A Triangle of Actions

Area of Science:

• Cardiology
• Pharmacology
• Endocrinology

Background:

• Doxorubicin (DOX) induces cardiotoxicity via RAAS activation, oxidative stress, and apoptosis.
• Cortisol influences metabolism, immunity, cardiovascular function, and drug pharmacokinetics via P-glycoprotein (P-gp).
• Apelin signaling, via APJ receptor, offers cardioprotective, antifibrotic, and anti-inflammatory effects.

Purpose of the Study:

• To explore the complex interplay between apelin and cortisol in the context of DOX-induced cardiotoxicity.
• To investigate how apelin-cortisol interactions influence RAAS and potential cardioprotective mechanisms.
• To identify potential therapeutic targets for mitigating anticancer drug-induced cardiac damage.

Main Methods:

• Narrative review of existing literature on apelin, cortisol, RAAS, and DOX cardiotoxicity.
• Analysis of molecular and cellular mechanisms involved in apelin-cortisol signaling.
• Exploration of the dual role of cortisol in inflammation and cardiac remodeling.

Main Results:

• Apelin signaling demonstrates protective effects against DOX cardiotoxicity by inhibiting RAAS and potentially reducing inflammation via short-term cortisol elevation.
• Chronically elevated cortisol, influenced by apelin, may contribute to cardiac remodeling and damage, particularly with altered 11β-HSD2 activity.
• The balance of apelin-cortisol interaction is critical in determining the net effect on cardiac health during DOX therapy.

Conclusions:

• Apelin-cortisol interplay presents a complex mechanism influencing DOX cardiotoxicity.
• Short-term cortisol elevation may be cardioprotective, while chronic elevation poses risks.
• Further research into these interactions is crucial for developing novel cardioprotective strategies in cancer therapy.