Key result
Apelin signaling protects against doxorubicin-induced cardiotoxicity by inhibiting RAAS and modulating cortisol pathways.
Why the study?
This narrative review was conducted to explore the molecular and cellular mechanisms of the interplay between apelin and cortisol in doxorubicin-induced cardiotoxicity.
Does the interplay between apelin and cortisol signaling modulate doxorubicin-induced cardiotoxicity in patients undergoing anticancer therapy?
Does the interplay between apelin and cortisol signaling modulate doxorubicin-induced cardiotoxicity in patients undergoing anticancer therapy?
This narrative review synthesizes the molecular mechanisms linking apelin, cortisol, and the RAAS in doxorubicin-induced cardiotoxicity, highlighting that while short-term apelin-mediated cortisol elevation may be cardioprotective via anti-inflammatory effects, chronic cortisol elevation and altered 11β-HSD2 activity may exacerbate myocardial remodeling and injury.
May support apelin pathway exploration in cardio-oncology; leaves open clinical translation pending prospective trials.
The mechanisms underlying doxorubicin (DOX) cardiotoxicity include activation of the renin–angiotensin–aldosterone system (RAAS), oxidative stress, mitochondrial dysfunction, calcium overload, and cardiomyocyte apoptosis. Cortisol plays a key role in regulating multiple metabolic, immunological, cardiovascular, and neuroendocrine processes and may additionally influence drug pharmacokinetics by modulating the activity of P-glycoprotein (P-gp). The peptide apelin, through its specific target, angiotensin II protein J receptor (APJ), exerts cardioprotective, antifibrotic, and anti-inflammatory effects. The available data demonstrate that apelin signaling protects against DOX-induced cardiotoxicity, impacts cortisol secretion, and inhibits RAAS. Short-term elevation in cortisol levels, caused by apelin, may reduce inflammation and thus have cardioprotective properties. However, through chronically elevated cortisol levels, apelin may indirectly contribute to peripheral resistance, cardiac remodeling, and myocardial damage, especially when cortisol metabolism by 11β-hydroxysteroid dehydrogenase 2 (11β-HSD2) is altered. This narrative review explores the potential molecular and cellular mechanisms shaping the outcome of apelin–cortisol interplay, offering a potential foundation for developing cardioprotective strategies during anticancer therapy. Future studies should be aimed at assessing the complex interactions between cortisol, apelin, and the RAAS regarding DOX-induced cardiotoxicity.
No takes yet. Share an insight, caveat, or question.
Dziobiak et al. (2026) conducted a review in Doxorubicin-induced cardiotoxicity. Apelin and cortisol interplay was evaluated. Apelin signaling protects against doxorubicin-induced cardiotoxicity via RAAS inhibition and acute cortisol modulation, whereas chronic cortisol exposure may promote adverse cardiac remodeling.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: