ArticleEMBO molecular medicine2024
Apelin-VEGF-C mRNA delivery as therapeutic for the treatment of secondary lymphedema.
Article in EMBO molecular medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
What it found
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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.
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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.
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Who cites it
9 citing papers in PubMed, 9 citations in OpenAlex.
- Therapeutic Potential of Lymphatic Endothelial Progenitor Cells in Secondary Lymphedema: A Preclinical Murine Study.Biomedicines · 2026Article
- Lymphatic Endothelial Cells in Health and Disease.MedComm · 2026Review
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- Keratinocytes: A key player in skin immunity and their emerging roles in secondary lymphedema.JID innovations : skin science from molecules to population health · 2026Review
- β-Arrestin1/2 are essential for embryonic lymphatic vessel development.JCI insight · 2026Article
- Cardiomyocyte-Derived Apelin Rescues Viral Myocarditis-Induced Cardiac Lymphatic Dysfunction and Remodeling.JACC. Basic to translational science · 2026Article
- Mechanisms and treatments of lymphedema.Frontiers in immunology · 2026Review
- lncRNA LINC-PINT controls lymphatic function and inflammatory profile in lymphedema.Science advances · 2025Article
- Tissue-Engineered Therapeutics for Lymphatic Regeneration: Solutions for Myocardial Infarction and Secondary Lymphedema.Advanced healthcare materials · 2025Review
Corrections and comments
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Authors and funding
19 authors at 5 institutions in 1 country.
Funding
Abstract
Secondary lymphedema (LD) corresponds to a severe lymphatic dysfunction leading to the accumulation of fluid and fibrotic adipose tissue in a limb. Here, we identified apelin (APLN) as a powerful molecule for regenerating lymphatic function in LD. We identified the loss of APLN expression in the lymphedematous arm compared to the normal arm in patients. The role of APLN in LD was confirmed in APLN knockout mice, in which LD is increased and associated with fibrosis and dermal backflow. This was reversed by intradermal injection of APLN-lentivectors. Mechanistically, APLN stimulates lymphatic endothelial cell gene expression and induces the binding of E2F8 transcription factor to the promoter of CCBE1 that controls VEGF-C processing. In addition, APLN induces Akt and eNOS pathways to stimulate lymphatic collector pumping. Our results show that APLN represents a novel partner for VEGF-C to restore lymphatic function in both initial and collecting vessels. As LD appears after cancer treatment, we validated the APLN-VEGF-C combination using a novel class of nonintegrative RNA delivery LentiFlash® vector that will be evaluated for phase I/IIa clinical trial.
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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 OpenQuestion graph.