scholarly journals miR-503/Apelin-12 mediates high glucose-induced microvascular endothelial cells injury via JNK and p38MAPK signaling pathway

2020 ◽  
Vol 14 ◽  
pp. 111-118 ◽  
Author(s):  
Kai Chen ◽  
Xin-Lan Zhao ◽  
Lang-Bo Li ◽  
Ling-Yun Huang ◽  
Zhuo Tang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Signaling Pathway ◽  
High Glucose ◽  
Microvascular Endothelial Cells ◽  
P38mapk Signaling ◽  
Microvascular Endothelial

scholarly journals Assessment of cellular mechanisms contributing to cAMP compartmentalization in pulmonary microvascular endothelial cells

2012 ◽  
Vol 302 (6) ◽  
pp. C839-C852 ◽  
Author(s):  
Wei P. Feinstein ◽  
Bing Zhu ◽  
Silas J. Leavesley ◽  
Sarah L. Sayner ◽  
Thomas C. Rich
Keyword(s):  
Endothelial Cells ◽  
Adenylyl Cyclase ◽  
Signaling Pathway ◽  
Camp Signaling ◽  
Microvascular Endothelial Cells ◽  
Camp Production ◽  
Barrier Integrity ◽  
Pulmonary Microvascular Endothelial Cells ◽  
Camp Signaling Pathway ◽  
Microvascular Endothelial

Cyclic AMP signals encode information required to differentially regulate a wide variety of cellular responses; yet it is not well understood how information is encrypted within these signals. An emerging concept is that compartmentalization underlies specificity within the cAMP signaling pathway. This concept is based on a series of observations indicating that cAMP levels are distinct in different regions of the cell. One such observation is that cAMP production at the plasma membrane increases pulmonary microvascular endothelial barrier integrity, whereas cAMP production in the cytosol disrupts barrier integrity. To better understand how cAMP signals might be compartmentalized, we have developed mathematical models in which cellular geometry as well as total adenylyl cyclase and phosphodiesterase activities were constrained to approximate values measured in pulmonary microvascular endothelial cells. These simulations suggest that the subcellular localizations of adenylyl cyclase and phosphodiesterase activities are by themselves insufficient to generate physiologically relevant cAMP gradients. Thus, the assembly of adenylyl cyclase, phosphodiesterase, and protein kinase A onto protein scaffolds is by itself unlikely to ensure signal specificity. Rather, our simulations suggest that reductions in the effective cAMP diffusion coefficient may facilitate the formation of substantial cAMP gradients. We conclude that reductions in the effective rate of cAMP diffusion due to buffers, structural impediments, and local changes in viscosity greatly facilitate the ability of signaling complexes to impart specificity within the cAMP signaling pathway.

Hydroxysafflor yellow A promotes angiogenesis in rat brain microvascular endothelial cells injured by oxygen-glucose deprivation/reoxygenation(OGD/R) through SIRT1-HIF-1α-VEGFA signaling pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Juxuan Ruan ◽  
Lei Wang ◽  
Jiheng Dai ◽  
Jing Li ◽  
Ning Wang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Growth Factor ◽  
Signaling Pathway ◽  
Ischemia Reperfusion ◽  
Tube Formation ◽  
Microvascular Endothelial Cells ◽  
Brain Microvascular Endothelial Cells ◽  
Hydroxysafflor Yellow A ◽  
Microvascular Endothelial

Objective: Angiogenesis led by brain microvascular endothelial cells (BMECs) contributes to the remission of brain injury after brain ischemia reperfusion. In this study, we investigated the effects of hydroxysafflor yellow A(HSYA) on angiogenesis of BMECs injured by OGD/R via SIRT1-HIF-1α-VEGFA signaling pathway. Methods: The OGD/R model of BMECs was established in vitro by OGD for 2h and reoxygenation for 24h. At first, the concentrations of vascular endothelial growth factor (VEGF), Angiopoietin (ang) and platelet-derived growth factor (PDGF) in supernatant were detected by ELISA, and the proteins expression of VEGFA, Ang-2 and PDGFB in BMECs were tested by western blot; the proliferation, adhesion, migration (scratch healing and transwell) and tube formation experiment of BMECs; the expression of CD31 and CD34 were tested by immunofluorescence staining. The levels of sirtuin1(SIRT1), hypoxia-inducible factor-1α (HIF-1α), VEGFA mRNA and protein were tested. Results: HSYA up-regulated the levels of VEGF, Ang and PDGF in the supernatant of BMECs under OGD/R, and the protein expression of VEGFA, Ang-2 and PDGFB were increased; HSYA could significantly alleviate the decrease of cell proliferation, adhesion, migration and tube formation ability of BMECs during OGD/R; HSYA enhanced the fluorescence intensity of CD31 and CD34 of BMECs during OGD/R; HSYA remarkably up-regulated the expression of SIRT1, HIF-1α, VEGFA mRNA and protein after OGD/R, and these increase decreased after SIRT1 was inhibited. Conclusion: SIRT1-HIF-1α-VEGFA signaling pathway is involved in HSYA improves angiogenesis of BMECs injured by OGD/R.

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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