ReviewFrontiers in immunology2026
The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.
Review in Frontiers in immunology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite advances in therapies targeting hemodynamic and neurohormonal axes in heart failure (HF), incomplete reverse remodeling (RR) characterized by persistent myocardial edema and fibrosis remains a major clinical challenge. This review posits that dysfunction of the cardiac lymphatic system, a critical but understudied pathway for interstitial fluid and immune cell clearance, constitutes a fundamental barrier to complete myocardial recovery. We synthesize current evidence outlining the anatomy, developmental biology, and physiological role of cardiac lymphatics in maintaining myocardial fluid homeostasis and immune surveillance. In the context of HF, the lymphatic system undergoes a dynamic evolution: an initial compensatory lymphangiogenic response in the acute phase facilitates the clearance of edema and inflammatory cells, while its subsequent exhaustion or impairment in chronic HF perpetuates a vicious cycle of inflammation, fibrosis, and adverse remodeling. Central molecular pathways, including the VEGF-C/VEGFR-3 axis and transcriptional regulators like PROX1/FOXC2, govern lymphatic growth, integrity, and function. Furthermore, lymphatics actively modulate post-injury immune responses via specialized mechanisms such as CCL21/CCR7-guided cell trafficking. Therapeutically, augmenting cardiac lymphangiogenesis presents a promising strategy to enhance fluid drainage, resolve maladaptive inflammation, and directly support cardiomyocyte survival, thereby creating a conducive milieu for RR. However, translating this potential requires overcoming translational hurdles related to intervention timing, comorbidity-specific lymphatic dysfunction, and the development of targeted delivery systems. This review concludes that harnessing the cardiac lymphatic system represents a paradigm-shifting therapeutic avenue, complementary to existing regimens, with the potential to promote more complete and sustainable reverse remodeling in heart failure.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.