Current heart failure reports · 2025
Endosomal Mechanisms in Heart Failure Pathophysiology.
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Hoes Martijn F, Wang Shujin, Luiken Joost Jfp
Аннотация
PURPOSE OF REVIEW: To examine the role of endosomal dysfunction in heart failure pathophysiology and evaluate its potential as a therapeutic target, particularly focusing on its regulation of cardiac metabolism.
RECENT FINDINGS: Endosomal dysfunction, driven by v-ATPase disassembly and loss of acidification, emerges as a key contributor to metabolic perturbations in heart failure. This dysfunction leads to uncontrolled CD36 translocation, resulting in lipotoxicity and inflammatory signaling through CD36-TLR4 complex formation. These mechanisms are especially relevant in diabetic cardiomyopathy and heart failure with preserved ejection fraction. The endosomal system represents a promising therapeutic target in heart failure, though its contribution varies among patients and disease stages. Recent advances in molecular imaging and biomarker analysis enable better patient stratification, opening new avenues for personalized endosome-targeted therapies in heart failure treatment.
RECENT FINDINGS: Endosomal dysfunction, driven by v-ATPase disassembly and loss of acidification, emerges as a key contributor to metabolic perturbations in heart failure. This dysfunction leads to uncontrolled CD36 translocation, resulting in lipotoxicity and inflammatory signaling through CD36-TLR4 complex formation. These mechanisms are especially relevant in diabetic cardiomyopathy and heart failure with preserved ejection fraction. The endosomal system represents a promising therapeutic target in heart failure, though its contribution varies among patients and disease stages. Recent advances in molecular imaging and biomarker analysis enable better patient stratification, opening new avenues for personalized endosome-targeted therapies in heart failure treatment.