Microcirculation (New York, N.Y. : 1994) · 2026
GLP-1 Receptors Are Enriched in the Lymphatic Endothelium and Their Pharmacological Activation With Semaglutide Improves the Pumping Capacity of Lymphatic Vessels.
СтатьяПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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Schulz Mary E, Akerstrom Victoria L, Dayan Joseph H, Castorena-Gonzalez Jorge A
Аннотация
OBJECTIVES: Recent clinical studies have suggested that glucagon-like peptide-1 receptor (GLP-1R) agonists may be effective therapies to treat or reduce the risk of developing secondary lymphedema. In this study, we aimed to (1) determine if GLP-1Rs are present in the lymphatic vasculature and characterize their expression, and (2) assess the effects of GLP-1R agonism on the contractile function of collecting lymphatic vessels.
METHODS: We assessed the expression of GLP-1Rs in and around the lymphatic vasculature by single-cell RNA sequencing and fluorescence confocal microscopy, and evaluated the direct effects of GLP-1R agonist, semaglutide, on modulating lymphatic contractility using pressure myography.
RESULTS: Expression of Glp1r (encoding GLP-1Rs) was detected exclusively in lymphatic endothelial cells. Pharmacological activation of GLP-1Rs led to robust vasodilation and an increase in the pumping capacity of isolated collecting lymphatics from WT, diet-induced obese, and hypercholesterolemic ApoE KO mice. The GLP-1R-mediated response was in part facilitated by nitric oxide and its potential interaction with NaV channels; however, additional signaling remains to be elucidated.
CONCLUSIONS: Our results revealed a direct, beneficial effect of GLP-1R agonism on lymphatic pumping capacity mediated by robust vasodilation, allowing lymphatics to accommodate and displace larger fluid volumes while maintaining strong and highly efficient contractions.
METHODS: We assessed the expression of GLP-1Rs in and around the lymphatic vasculature by single-cell RNA sequencing and fluorescence confocal microscopy, and evaluated the direct effects of GLP-1R agonist, semaglutide, on modulating lymphatic contractility using pressure myography.
RESULTS: Expression of Glp1r (encoding GLP-1Rs) was detected exclusively in lymphatic endothelial cells. Pharmacological activation of GLP-1Rs led to robust vasodilation and an increase in the pumping capacity of isolated collecting lymphatics from WT, diet-induced obese, and hypercholesterolemic ApoE KO mice. The GLP-1R-mediated response was in part facilitated by nitric oxide and its potential interaction with NaV channels; however, additional signaling remains to be elucidated.
CONCLUSIONS: Our results revealed a direct, beneficial effect of GLP-1R agonism on lymphatic pumping capacity mediated by robust vasodilation, allowing lymphatics to accommodate and displace larger fluid volumes while maintaining strong and highly efficient contractions.