ArticleThe American journal of pathology2020
The Renin-Angiotensin-Aldosterone System (RAAS) Is One of the Effectors by Which Vascular Endothelial Growth Factor (VEGF)/Anti-VEGF Controls the Endothelial Cell Barrier.
Article in The American journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 35 citations in OpenAlex.
- Prevention is better than cure: role of RAAS blockade in preventing catastrophic hypotension after bilateral native nephrectomies in infants.Pediatric nephrology (Berlin, Germany) · 2026Article
- Bradykinin reduces wound healing in human umbilical vein endothelial cells via downregulation of vascular endothelial growth factor A.Journal of inflammation (London, England) · 2026Article
- Prevalence of Hypertensive Disorders of Pregnancy and Associated Birth Outcomes Among Adolescent Mothers at a Tertiary Hospital in Zambia: A Retrospective Cross-Sectional Study.International journal of hypertension · 2026Article
- Proteome atlas for mechanistic discovery and risk prediction of diabetic retinopathy.Nature communications · 2025Article
- Proliferative diabetic retinopathy subtypes defined by immune defense and endothelial mitochondrial dysfunction.Signal transduction and targeted therapy · 2025Article
- The status of studies on the mechanism of microcirculatory dysfunction in the process of diabetic kidney injury.Diabetology & metabolic syndrome · 2025Review
- The novel antidiabetic medications on diabetic retinopathy: relevant molecular mechanisms, advancing diagnostic innovations, and therapeutic implications.Frontiers in medicine · 2025Review
- Effects of regular, glulisine, and aspart insulin on vascular endothelial growth factor and angiotensinogen expression in hyperglycemic retinal pigment epithelial (RPE) and human retinal endothelial cells (HRECs).Frontiers in ophthalmology · 2025Article
- RAAS in diabetic retinopathy: mechanisms and therapies.Archives of endocrinology and metabolism · 2024Review
- Correlation of ACE gene polymorphisms and platelet parameters with morning peak blood pressure in hypertensive patients.American journal of translational research · 2024Article
- RAAS-deficient organoids indicate delayed angiogenesis as a possible cause for autosomal recessive renal tubular dysgenesis.Nature communications · 2023Article
- Different responses of the MIO‑M1 Mueller cell line to angiotensin II under hyperglycemic or hypoxic conditions.Biomedical reports · 2023Article
- The Multi-Kinase Inhibitor RepSox Enforces Barrier Function in the Face of Both VEGF and Cytokines.Biomedicines · 2023Article
- Activin A Limits VEGF-Induced Permeability via VE-PTP.International journal of molecular sciences · 2023Article
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- VEGF Induces Expression of Genes That Either Promote or Limit Relaxation of the Retinal Endothelial Barrier.International journal of molecular sciences · 2023Article
- The role of aldosterone in the pathogenesis of diabetic retinopathy.Frontiers in endocrinology · 2023Review
- Hyperglycemia Promotes Mitophagy and Thereby Mitigates Hyperglycemia-Induced Damage.The American journal of pathology · 2022Article
- Risk factor analysis and clinical decision tree model construction for diabetic retinopathy in Western China.World journal of diabetes · 2022Article
- Modified Qing' e Pills exerts anti-osteoporosis effects and prevents bone loss by enhancing type H blood vessel formation.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Leakage of retinal blood vessels, which is an essential element of diabetic retinopathy, is driven by chronic elevation of vascular endothelial growth factor (VEGF). VEGF quickly relaxes the endothelial cell barrier by triggering signaling events that post-translationally modify pre-existing components of intercellular junctions. VEGF also changes expression of genes that are known to regulate barrier function. Our goal was to identify effectors by which VEGF and anti-VEGF control the endothelial cell barrier in cells that were chronically exposed to VEGF (hours instead of minutes). The duration of VEGF exposure influenced both barrier relaxation and anti-VEGF-mediated closure. Most VEGF-induced changes in gene expression were not reversed by anti-VEGF. Those that were constitute VEGF effectors that are targets of anti-VEGF. Pursuit of such candidates revealed that VEGF used multiple, nonredundant effectors to relax the barrier in cells that were chronically exposed to VEGF. One such effector was angiotensin-converting enzyme, which is a member of the renin-angiotensin-aldosterone system (RAAS). Pharmacologically antagonizing either the angiotensin-converting enzyme or the receptor for angiotensin II attenuated VEGF-mediated relaxation of the barrier. Finally, activating the RAAS reduced the efficacy of anti-VEGF. These discoveries provide a plausible mechanistic explanation for the long-standing appreciation that RAAS inhibitors are beneficial for patients with diabetic retinopathy and suggest that antagonizing the RAAS improves patients' responsiveness to anti-VEGF.
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