ArticleEuropean heart journal2023
A2AR-mediated lymphangiogenesis via VEGFR2 signaling prevents salt-sensitive hypertension.
Article in European heart journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 29 citations in OpenAlex.
- Adenosine receptor signaling in vascular diseases: from molecular mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2026Review
- Salt and chronic kidney disease.Nature reviews. Nephrology · 2026Review
- Ionic Extracts of Magnesium Powders Promote In Vitro Lymphangiogenesis.Biomedicines · 2026Article
- Sparcl1 mitigates abdominal aortic aneurysm through inhibiting lymphangiogenesis-mediated TLS formation.Nature immunology · 2026Article
- Deep learning-driven immunohistochemical analysis of renal lymphatics for chronic kidney disease: bioinformatic and histopathological study.Journal of pathology and translational medicine · 2026Article
- A Real-World Pharmacovigilance Study of Fruquintinib Based on the FDA Adverse Event Reporting System (FAERS) Database.Cancer medicine · 2025Article
- Cystatin F-a key player in central nervous system disease.Journal of neuroinflammation · 2025Review
- Regulation of transcription factor function by purinergic signalling in cardiovascular diseases.Purinergic signalling · 2025Review
- Mesenchymal stem cell therapy for breast cancer-related secondary lymphedema (Review).Molecular and clinical oncology · 2025Review
- Macrophage A2aR Alleviates LPS-Induced Vascular Endothelial Injury and Inflammation via Inhibiting M1 Polarisation and Oxidative Stress.Journal of cellular and molecular medicine · 2025Article
- Sodium-Directed Crosstalk Between Immune Cells and Lymphatic Vessels.Current hypertension reports · 2025Review
- Adenosine and adenosine receptors: a "double-edged sword" in cardiovascular system.Frontiers in pharmacology · 2025Review
- Huiyang Shengji Unguent Promotes Lymphangiogenesis and Wound Healing in Diabetic Chronic Wounds: Combined Insights from Proteomics and in vivo and in vitro Analyses.Journal of inflammation research · 2025Article
- Crosstalk between fat tissue and muscle, brain, liver, and heart in obesity: cellular and molecular perspectives.European journal of medical research · 2024Review
- EphrinB2-mediated CDK5/ISL1 pathway enhances cardiac lymphangiogenesis and alleviates ischemic injury by resolving post-MI inflammation.Signal transduction and targeted therapy · 2024Article
- Immune and inflammatory mechanisms in hypertension.Nature reviews. Cardiology · 2024Review
- Lymph vessels, NaNature reviews. Nephrology · 2023Article
- Role of Lymphangiogenesis in Cardiac Repair and Regeneration.Methodist DeBakey cardiovascular journal · 2023Review
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16 authors at 5 institutions in 3 countries.
Funding
Abstract
aimsExcess dietary sodium intake and retention lead to hypertension. Impaired dermal lymphangiogenesis and lymphatic dysfunction-mediated sodium and fluid imbalance are pathological mechanisms. The adenosine A2A receptor (A2AR) is expressed in lymphatic endothelial cells (LECs), while the roles and mechanisms of LEC-A2AR in skin lymphangiogenesis during salt-induced hypertension are not clear. METHODS AND
resultsThe expression of LEC-A2AR correlated with lymphatic vessel density in both high-salt diet (HSD)-induced hypertensive mice and hypertensive patients. Lymphatic endothelial cell-specific A2AR knockout mice fed HSD exhibited 17 ± 2% increase in blood pressure and 17 ± 3% increase in Na+ content associated with decreased lymphatic density (-19 ± 2%) compared with HSD-WT mice. A2AR activation by agonist CGS21680 increased lymphatic capillary density and decreased blood pressure in HSD-WT mice. Furthermore, this A2AR agonist activated MSK1 directly to promote VEGFR2 activation and endocytosis independently of VEGF as assessed by phosphoprotein profiling and immunoprecipitation assays in LECs. VEGFR2 kinase activity inhibitor fruquintinib or VEGFR2 knockout in LECs but not VEGF-neutralizing antibody bevacizumab suppressed A2AR activation-mediated decrease in blood pressure. Immunostaining revealed phosphorylated VEGFR2 and MSK1 expression in the LECs were positively correlated with skin lymphatic vessel density and A2AR level in hypertensive patients.
conclusionThe study highlights a novel A2AR-mediated VEGF-independent activation of VEGFR2 signaling in dermal lymphangiogenesis and sodium balance, which might be a potential therapeutic target in salt-sensitive hypertension.
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