YAP1 is required for the angiogenesis in retinal microvascular endothelial cells via the inhibition of MALAT1‐mediated miR‐200b‐3p in high glucose‐induced diabetic retinopathy

2019 ◽  
Vol 235 (2) ◽  
pp. 1309-1320 ◽  
Author(s):  
Ning Han ◽  
Wen Tian ◽  
Na Yu ◽  
Li Yu
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial

scholarly journals miR-146a Attenuates Inflammatory Pathways Mediated by TLR4/NF-κB and TNFαto Protect Primary Human Retinal Microvascular Endothelial Cells Grown in High Glucose

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Eun-Ah Ye ◽  
Jena J. Steinle
Keyword(s):  
Endothelial Cells ◽  
Diabetic Retinopathy ◽  
High Glucose ◽  
Microvascular Endothelial Cells ◽  
Inflammatory Pathways ◽  
Retinal Pathology ◽  
Cellular Pathways ◽  
Microvascular Endothelial ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

Pathological mechanisms underlying diabetic retinopathy are still not completely understood. Increased understanding of potential cellular pathways responsive to hyperglycemia is essential to develop novel therapeutic strategies for diabetic retinopathy. A growing body of evidence shows that microRNA (miRNA) play important roles in pathological mechanisms involved in diabetic retinopathy, as well as possessing potential as novel therapeutic targets. The hypothesis of this study was that miR-146a plays a key role in attenuating hyperglycemia-induced inflammatory pathways through reduced TLR4/NF-κB and TNFαsignaling in primary human retinal microvascular endothelial cells (REC). We cultured human REC in normal (5 mM) glucose or transferred to high glucose medium (25 mM) for 3 days. Transfection was performed on REC with miRNA mimic (hsa-miR-146a-5p). Our results demonstrate that miR-146a expression was decreased in human REC cultured in high glucose. Overexpression of miR-146a using mimics reduced the levels of TLR4/NF-κB and TNFαin REC cultured in high glucose. Both MyD88-dependent and -independent signaling were decreased by miR-146a overexpression in REC in high glucose conditions. The results suggest that miR-146a is a potential therapeutic target for reducing inflammation in REC through inhibition of TLR4/NF-κB and TNFα. Our study will contribute to understanding of diabetic retinal pathology, as well as providing important clues to develop therapeutics for clinical applications.

Autophagy inhibits high glucose induced cardiac microvascular endothelial cells apoptosis by mTOR signal pathway

APOPTOSIS ◽  
2017 ◽  
Vol 22 (12) ◽  
pp. 1510-1523 ◽  
Author(s):  
Zheng Zhang ◽  
Shenwei Zhang ◽  
Yong Wang ◽  
Ming Yang ◽  
Ning Zhang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
High Glucose ◽  
Signal Pathway ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

Abstract 269: Exendin-4 Prevents Glucose-induced Secretion of Tissue Transglutaminase-2 from Cardiac Microvascular Endothelial Cells: Potential Role in the Prevention of Matrix Remodeling in Diabetes

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Ali S Shihab ◽  
Vanitra A Richardson ◽  
Betsy B Dokken
Keyword(s):  
Endothelial Cells ◽  
Protein Expression ◽  
High Glucose ◽  
Tissue Transglutaminase ◽  
Vascular Complications ◽  
Transglutaminase 2 ◽  
Conditioned Media ◽  
Microvascular Endothelial Cells ◽  
Microvascular Endothelial ◽  
Cardiac Microvascular Endothelial Cells

Diabetes causes endothelial dysfunction, which is the initial trigger for vascular complications in diabetic patients. Hyperglycemia initiates a cascade of events that alters protein expression and secretion by endothelial cells. Tissue transglutaminase-2 (tTG2) is an enzyme that under physiologic conditions is sequestered inside the endothelial cell, but under pathologic conditions causing decreased bioavailability of nitric oxide, tTG2 is secreted, activated, and catalyzes irreversible crosslinking of proteins in the extracellular matrix (ECM). Exendin-4 (Ex-4) is a glucagon-like peptide-1 receptor (GLP-1R) agonist, used in the treatment of type 2 diabetes, which has vasculo-protective effects. We hypothesized that hyperglycemic stress would induce secretion of tTG2, and that this effect would be attenuated by Ex-4. Mouse cardiac microvascular endothelial cells (MCECs) were serum-starved and exposed to control (5.5 mM glucose) or hyperglycemic (25 mM glucose) conditions, with or without Ex-4 (10 nM) x 72 hrs. Proteins from conditioned media were isolated, trypsinized, and analyzed using LC-MS/MS (LTQ Orbitrap Velos). Immunoblots from cell homogenate were probed for tTG protein expression. Conditioned media from MCECs exposed to high-glucose but not Ex-4 contained tTG2, which was absent in media from cells exposed to high-glucose and Ex-4, as well as in media from control cells, suggesting that Ex-4 prevented the secretion of tTG2 induced by hyperglycemic stress. Protein expression in cell lysate was not different. These findings may have important implications for the etiology of diabetic vascular complications, and for the role of Ex-4 to prevent the pathologic ECM remodeling associated with diabetic vasculopathy. Further studies are ongoing to determine the mechanisms of glucose-induced secretion of tTG2, as well as the mechanisms by which Ex-4 prevents this effect.

Abstract 235: Hypoxia Enhanced Delivery of Mitochondria-Targeted Catalase Protects Choroid Retinal Microvascular Endothelial Cells from Oxidative Stress

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christopher J Dougherty ◽  
Howard Prentice ◽  
Kathleen Dorey ◽  
Keith A Webster ◽  
Janet C Blanks
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Endothelial Cell ◽  
High Glucose ◽  
Endothelial Permeability ◽  
Luciferase Assay ◽  
Expression Vectors ◽  
Microvascular Endothelial Cells ◽  
Tissue Specific ◽  
Microvascular Endothelial

Loss of pericytes is a critical event early in the progression of microvascular dysfunction in diabetic retinopathy. Pericyte loss may be linked to high glucose mediated reactive oxygen species generation, blocking N-cadherin trafficking to the endothelial cell surface preventing pericyte recruitment and vessel stabilization. Hydrogen peroxide has been identified as a major free radical produced during high glucose exposure in endothelial cells. The goal of this research is to determine if tissue-specific hypoxia-regulated expression of a mitochondria-targeted catalase can prevent or limit RF/6A microvascular endothelial cell apoptosis and decrease vascular permeability by limiting cellular oxidative stress. For the development of tissue-specific and hypoxia-enhanced expression vectors, promoters were constructed with nine tandem combinations of HREs. This 9x HRE oligomer enhancer was inserted together into a pGL3 firefly luciferase plasmid with the Tie2( short ) promoter for endothelial-specific expression. The 9xHRE-Tie2( sh ) promoter construct was highly selective for RF/6A cells producing a basal amount of mitochondria-targeted catalase equivalent to the Tie2( short ) promoter alone. In response to hypoxia ( pO 2 = 1% ), the 9xHRE-Tie2( short ) promoter showed a 21-fold hypoxia-inducible activation similar in strength to the CMV promoter , measured by dual luciferase assay. The hybrid promoters were incorporated into a replication deficient AAV delivery system for apoptosis and cell culture based endothelial permeability assays. In preliminary assays using RF/6A microvascular endothelial cells, apoptosis was reduced by 58% and permeability was reduced by 46%. The results suggest that mitochondria-targeted catalase protects RF/6A microvascular endothelial cells from apoptosis and reduces endothelial permeability in a high-glucose, low-oxygen environment.

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