ArticleProceedings of the National Academy of Sciences of the United States of America2016
Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 67 citations in OpenAlex.
- Lipoprotein (a) in the Development and Progression of Diabetic Retinopathy: A Systematic Review and Meta-Analysis.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Phospholipases: Where Do We Stand?Methods in molecular biology (Clifton, N.J.) · 2027Review
- Lipoprotein-associated phospholipase A2 (Lp-PLA2): a key hub linking lipid metabolism and immune inflammation.Frontiers in immunology · 2026Review
- Development and Novel Therapeutics in Diabetic Retinopathy.Current diabetes reviews · 2026Review
- Proteomic Exploration of L1CAMInternational journal of molecular sciences · 2025Article
- PLA2G7 promotes immune evasion of bladder cancer through the JAK-STAT-PDL1 axis.Cell death & disease · 2025Article
- Discovering biomarkers for chronic sinusitis with nasal polyps: a study integrating bioinformatics analysis and experimental validation of macrophage polarization and metabolism-related genes.Frontiers in bioinformatics · 2025Article
- Clinical value of Lp-PLA2, LDL-C, HDL-C, hs-CRP, leukocyte, FPG and HbA1c in type 2 diabetes mellitus patients with acute ischemic stroke.Frontiers in endocrinology · 2025Article
- Lipidomic studies revealing serological markers associated with the occurrence of retinopathy in type 2 diabetes.Journal of translational medicine · 2024Article
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- Inhibiting PLA2G7 reverses the immunosuppressive function of intratumoral macrophages and augments immunotherapy response in hepatocellular carcinoma.Journal for immunotherapy of cancer · 2024Article
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- Higher serum Lp-PLA2 is associated with cognitive impairment in Parkinson's disease patients.Frontiers in neuroscience · 2024Article
- Review
- Pharmacotherapy and Nutritional Supplements for Neovascular Eye Diseases.Medicina (Kaunas, Lithuania) · 2023Review
- Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities - preliminary data for PPPM validation.The EPMA journal · 2023Article
- Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy.International journal of molecular sciences · 2023Article
- Diagnostic circulating biomarkers to detect vision-threatening diabetic retinopathy: Potential screening tool of the future?Acta ophthalmologica · 2022Review
- Targeting Plasma Kallikrein With a Novel Bicyclic Peptide Inhibitor (THR-149) Reduces Retinal Thickening in a Diabetic Rat Model.Investigative ophthalmology & visual science · 2021Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.
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