Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting.
- 1Department of Cardiology, Ma'anshan People's Hospital, Wannan Medical University, Anhui Ma'anshan, 243099, China.
- 2Graduate School, Wannan Medical University, Anhui Wuhu, 241002, China.
- 3Department of Cardiology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Anhui Hefei, 230001, China.
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.
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BibTeX
@article{zhang2026crosscutting,
title = {{Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting.}},
author = {KaiJian Zhang and Hui Li and Wei Wen and BuChun Zhang},
journal = {International journal of biological sciences},
year = {2026},
month = sep,
doi = {10.7150/ijbs.137328},
url = {https://europepmc.org/article/MED/42910211},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cross-cutting circuits in heart failure with preserved ejection fraction: Integrating adipokine biology, mechanotransduction, and precision targeting.
AU - KaiJian Zhang
AU - Hui Li
AU - Wei Wen
AU - BuChun Zhang
PY - 2026
DA - 2026/09/11
JO - International journal of biological sciences
DO - 10.7150/ijbs.137328
UR - https://europepmc.org/article/MED/42910211
AB - 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.
SN - 1449-2288
ER -