Work

Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting

Year: 2026

Type: review

Abstract: Background: Heart failure with preserved ejection fraction (HFpEF) accounts for half of all heart failure cases. However, its complex pathophysiology, which is characterized by bidirectional interactions among immune, metabolic, and mechanical pathways, has long resisted a simple explanation. Approach: Rather than listing parallel mechanisms, this review organizes recent breakthroughs around three cross-cutting frontiers: neuroimmune regulation, cell-type-specific metabolic reprogramming, and mechanotransduction. It then integrates these frontiers within the adipokine hypothesis. Key findings: Cardiac macrophage subset imbalance, myeloid fatty acid-driven inflammation, matrix stiffness-mediated feedforward loops, and adipokine imbalance have emerged as interconnected drivers of HFpEF. Conclusion: With the aid of multi-omics and machine learning, mapping these mechanistic dialogues onto phenotype-targeted precision therapy provides a roadmap for transforming HFpEF from a syndrome defined by ejection fraction into molecularly tractable endotypes.

Source: International Journal of Biological Sciences

DOI: 10.7150/ijbs.137328

Authors: KaiJian Zhang, Hui Li, Wei Wen, BuChun Zhang

Institutions: Wannan Medical College, University of Science and Technology of China

Language: English

Topic: Cardiac Fibrosis and Remodeling

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,337