ArticlePloS one2019
Inhibition of Ephrin-B2 in brain pericytes decreases cerebral pathological neovascularization in diabetic rats.
Article in PloS one, 2019. 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, 31 citations in OpenAlex.
- SARS-CoV-2 Spike Protein Exacerbates Thromboembolic Cerebrovascular Complications in Humanized ACE2 Mouse Model.Translational stroke research · 2025Article
- Exploring the key target molecules of angiogenesis in diabetic cardiomyopathy based on bioinformatics analysis.Frontiers in endocrinology · 2025Article
- Platelet-derived growth factor signaling in pericytes promotes hypothalamic inflammation and obesity.Molecular medicine (Cambridge, Mass.) · 2024Article
- SARS-CoV-2 Spike Protein Intensifies Cerebrovascular Complications in Diabetic hACE2 Mice through RAAS and TLR Signaling Activation.International journal of molecular sciences · 2023Article
- GLP-1 receptor nitration contributes to loss of brain pericyte function in a mouse model of diabetes.Diabetologia · 2022Article
- Cellular loci involved in the development of brain arteriovenous malformations.Frontiers in human neuroscience · 2022Review
- Short regulatory DNA sequences to target brain endothelial cells for gene therapy.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Not All Lectins Are Equally Suitable for Labeling Rodent Vasculature.International journal of molecular sciences · 2021Article
- Three-dimensional remodeling of functional cerebrovascular architecture and gliovascular unit in leptin receptor-deficient mice.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Cerebrovascular development: mechanisms and experimental approaches.Cellular and molecular life sciences : CMLS · 2021Review
- Pharmic Activation of PKG2 Alleviates Diabetes-Induced Osteoblast Dysfunction by Suppressing PLCOxidative medicine and cellular longevity · 2021Article
- Ephrin-Eph Signaling as a Novel Neuroprotection Path in Ischemic Stroke.Journal of molecular neuroscience : MN · 2020Review
- Ephrin B2 mediates high glucose induced endothelial-to-mesenchymal transition in human aortic endothelial cells.Cardiovascular diagnosis and therapy · 2020Article
- Increased Ephrin-B2 expression in pericytes contributes to retinal vascular death in rodents.Vascular pharmacology · 2020Article
- Multifaceted roles of pericytes in central nervous system homeostasis and disease.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Review
- This was the year that was: brain barriers and brain fluid research in 2019.Fluids and barriers of the CNS · 2020Article
- Immunomodulatory Approaches in Diabetes-Induced Cardiorenal Syndromes.Frontiers in cardiovascular medicine · 2020Review
- Brain Vasculature and Cognition.Arteriosclerosis, thrombosis, and vascular biology · 2019Review
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
We have previously shown that diabetes causes dysfunctional cerebral neovascularization that increases the risk for cerebrovascular disorders such as stroke and cognitive impairment. Pericytes (PCs) play a pivotal role in the angiogenic process through their interaction with the endothelial cells (EC). Yet, the role of PCs in dysfunctional cerebral neovascularization in diabetes is unclear. In the present study, we tested the hypothesis that the increased proangiogenic Ephrin-B2 signaling in PCs contributes to the dysfunctional cerebral neovascularization in diabetes. Type-II diabetes was induced by a combination of high fat diet and low dose streptozotocin injection in male Wistar rats. Selective in vivo Ephrin-B2 silencing in brain PCs was achieved using the stereotactic injection of adeno-associated virus (AAV) with NG2-promoter that expresses Ephrin-B2 shRNA. Neovascularization was assessed using vascular fluorescent dye stain. Novel object recognition (NOR) test was used to determine cognitive functions. Human brain microvascular pericytes HBMVPCs were grown in high glucose 25 mM and palmitate 200 uM (HG/Pal) to mimic diabetic conditions. Scratch migration and tube formation assays were conducted to evaluate PC/EC interaction and angiogenic functions in PC/EC co-culture. Diabetes increased the expression of Ephrin-B2 in the cerebrovasculature and pericytes. Concomitant increases in cerebral neovascularization parameters including vascular density, tortuosity and branching density in diabetic rats were accompanied by deterioration of cognitive function. Inhibition of Ephrin-B2 expression in PCs significantly restored cerebral vascularization and improved cognitive functions. HG/Pal increased PC/EC angiogenic properties in co-culture. Silencing Ephrin-B2 in PCs significantly reduced PC migration and PC/EC co-culture angiogenic properties. This study emphasizes the significant contribution of PCs to the pathological neovascularization in diabetes. Our findings introduce Ephrin-B2 signaling as a promising therapeutic target to improve cerebrovascular integrity in diabetes.
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