ArticleCardiovascular research2015
Lymphatic vascular integrity is disrupted in type 2 diabetes due to impaired nitric oxide signalling.
Article in Cardiovascular research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers.
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97 citing papers in PubMed, 139 citations in OpenAlex.
- Single-cell transcriptomic profiling reveals PDK4 upregulation and impaired VEGF-C/VEGFR3 signaling in cardiac lymphatic endothelial cells in diabetic cardiomyopathy.Molecular medicine (Cambridge, Mass.) · 2026Article
- Numerical modeling of fluid exchange between a collecting lymphatic vessel and the surrounding tissue.Journal of mathematical biology · 2026Article
- GLP-1 Receptors Are Enriched in the Lymphatic Endothelium and Their Pharmacological Activation With Semaglutide Improves the Pumping Capacity of Lymphatic Vessels.Microcirculation (New York, N.Y. : 1994) · 2026Article
- Dysfunctional adipose tissue-lymphatic crosstalk in obesity.Nature reviews. Endocrinology · 2026Review
- Guidelines for evaluating endothelial function in vascular tissue.American journal of physiology. Heart and circulatory physiology · 2026Review
- Why are SGLT2 inhibitors effective in HFpEF? Implications for interstitial fluid retention and cardio-renal interaction.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Review
- Impaired lymphangiogenesis in pericoronary adipose tissue correlates with diabetes-aggravated coronary atherosclerosis.Cardiovascular diabetology · 2026Article
- Unraveling lipedema: comprehensive insights and the path to future discoveries.npj metabolic health and disease · 2026Review
- The role of the cardiac lymphatic system in heart failure "reverse remodeling": from developmental signals to druggable targets.Frontiers in immunology · 2026Review
- Review
- Defective lymphatic vasculature in obesity.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- Metabolic and Immune Crosstalk in Cardiovascular Disease.Circulation research · 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
- Leukocyte-lymphatic intersections during cardiac inflammation.Journal of molecular and cellular cardiology · 2025Review
- Chronic metabolic stress impairs lymphatic contractility via activation of KATP channels in a mouse model of Type-2 diabetes.Frontiers in physiology · 2025Article
- Acute Metabolic Stress Induces Lymphatic Dysfunction Through KATP Channel Activation.Function (Oxford, England) · 2024Article
- Connexin-45 is expressed in mouse lymphatic endothelium and required for lymphatic valve function.JCI insight · 2024Article
- Piezo1 regulates meningeal lymphatic vessel drainage and alleviates excessive CSF accumulation.Nature neuroscience · 2024Article
- Lymphangiogenesis: A new strategy for heart disease treatment (Review).International journal of molecular medicine · 2024Review
- Current and Developing Lymphatic Imaging Approaches for Elucidation of Functional Mechanisms and Disease Progression.Molecular imaging and biology · 2024Review
37 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
aimsLymphatic vessel dysfunction is an emerging component of metabolic diseases and can lead to tissue lipid accumulation, dyslipidaemia, and oedema. While lymph leakage has been implicated in obesity and hypercholesterolaemia, whether similar lymphatic dysfunction exists in diabetes has not been investigated. METHODS AND
resultsTo measure the lymphatic integrity of transgenic mice, we developed a new assay that quantifies the solute permeability of murine collecting lymphatic vessels. Compared with age-matched wild-type (WT) controls, the permeability of collecting lymphatics from diabetic, leptin receptor-deficient (db/db) mice was elevated >130-fold. Augmenting nitric oxide (NO) production by suffusion of l-arginine rescued this defect. Using pharmacological tools and eNOS(-/-) mice, we found that NO increased WT lymphatic permeability, but reduced db/db lymphatic permeability. These conflicting actions of NO were reconciled by the finding that phosphodiesterase 3 (PDE3), normally inhibited by NO signalling, was active in db/db lymphatics and inhibition of this enzyme restored barrier function.
conclusionIn conclusion, we identified the first lymphatic vascular defect in type 2 diabetes, an enhanced permeability caused by low NO bioavailability. Further, this demonstrates that PDE3 inhibition is required to maintain lymphatic vessel integrity and represents a viable therapeutic target for lymphatic endothelial dysfunction in metabolic disease.
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