Molecular Mechanisms of Oxidative Stress‐induced STAT3 Activation in Endothelial Cells

Angiogenesis is the process of new vessel formation, which sprouts from preexisting vessels. This process is highly complex and primarily involves several key steps, including stimulation of endothelial cells by growth factors, degradation of the extracellular matrix by proteolytic enzymes, migration and proliferation of endothelial cells, and capillary tube formation. Currently, it is considered that multiple cytokines play a vital role in this process, which consist of proangiogenic factors (e.g., vascular endothelial growth factor, fibroblast growth factors, and angiopoietins) and antiangiogenic factors (e.g., endostatin, thrombospondin, and angiostatin). Angiogenesis is essential for most physiological events, such as body growth and development, tissue repair, and wound healing. However, uncontrolled neovascularization may contribute to angiogenic disorders. In physiological conditions, the above promoters and inhibitors function in a coordinated way to induce and sustain angiogenesis within a limited period of time. Conversely, the imbalance between proangiogenic and antiangiogenic factors could cause pathological angiogenesis and trigger several diseases. With insights into the molecular mechanisms of angiogenesis, increasing reports have shown that a close relationship exists between angiogenesis and oxidative stress (OS) in both physiological and pathological conditions. OS, an imbalance between prooxidant and antioxidant systems, is a cause and consequence of many vascular complains and serves as one of the biomarkers for these diseases. Furthermore, emerging evidence supports that OS and angiogenesis play vital roles in many dermatoses, such as psoriasis, atopic dermatitis, and skin tumor. This review summarizes recent findings on the role of OS as a trigger of angiogenesis in skin disorders, highlights newly identified mechanisms, and introduces the antiangiogenic and antioxidant therapeutic strategies.

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MOLECULAR MECHANISMS OF THE ACTIVATION BY OXIDATIVE STRESS OF INTRACELLULAR ANTIOXIDANT IN VASCULAR ENDOTHELIAL CELLS

Anesthesiology ◽

10.1097/00000542-199809050-00014 ◽

1998 ◽

Vol 89 (Supplement) ◽

pp. 202A

Author(s):

S. Cho ◽

K. Sakai ◽

K. Sumikawa

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Molecular Mechanisms ◽

Vascular Endothelial Cells ◽

Vascular Endothelial

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How AMPK and PKA Interplay to Regulate Mitochondrial Function and Survival in Models of Ischemia and Diabetes

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/4353510 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 15

Author(s):

Jingdian Zhang ◽

Yumeng Wang ◽

Xiaofeng Liu ◽

Ruben K. Dagda ◽

Ying Zhang

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Cardiovascular Diseases ◽

Protein Kinase ◽

Cell Survival ◽

Mitochondrial Function ◽

Molecular Mechanisms ◽

Temporal Dynamics ◽

Protein Translation ◽

Conservation Of Energy

Adenosine monophosphate-activated protein kinase (AMPK) is a conserved, redox-activated master regulator of cell metabolism. In the presence of oxidative stress, AMPK promotes cytoprotection by enhancing the conservation of energy by suppressing protein translation and by stimulating autophagy. AMPK interplays with protein kinase A (PKA) to regulate oxidative stress, mitochondrial function, and cell survival. AMPK and dual-specificity A-kinase anchoring protein 1 (D-AKAP1), a mitochondrial-directed scaffold of PKA, interact to regulate mitochondrial function and oxidative stress in cardiac and endothelial cells. Ischemia and diabetes, a chronic disease that increases the onset of cardiovascular diseases, suppress the cardioprotective effects of AMPK and PKA. Here, we review the molecular mechanisms by which AMPK and D-AKAP1/PKA interplay to regulate mitochondrial function, oxidative stress, and signaling pathways that prime endothelial cells, cardiac cells, and neurons for cytoprotection against oxidative stress. We discuss recent literature showing how temporal dynamics and localization of activated AMPK and PKA holoenzymes play a crucial role in governing cellular bioenergetics and cell survival in models of ischemia, cardiovascular diseases, and diabetes. Finally, we propose therapeutic strategies that tout localized PKA and AMPK signaling to reverse mitochondrial dysfunction, oxidative stress, and death of neurons and cardiac and endothelial cells during ischemia and diabetes.

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Integrated investigation of lipidome and related signaling pathways uncovers molecular mechanisms of tetramethylpyrazine and butylidenephthalide protecting endothelial cells under oxidative stress

Molecular BioSystems ◽

10.1039/c2mb05510d ◽

2012 ◽

Vol 8 (6) ◽

pp. 1789 ◽

Cited By ~ 12

Author(s):

Jie Yang ◽

Song Yang ◽

Ying-Jin Yuan

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Signaling Pathways ◽

Molecular Mechanisms

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EndMT Regulation by Small RNAs in Diabetes-Associated Fibrotic Conditions: Potential Link With Oxidative Stress

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.683594 ◽

2021 ◽

Vol 9 ◽

Author(s):

Roberta Giordo ◽

Yusra M. A. Ahmed ◽

Hilda Allam ◽

Salah Abusnana ◽

Lucia Pappalardo ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Small Rnas ◽

Molecular Mechanisms ◽

Type I Collagen ◽

Current Knowledge ◽

Common Denominator ◽

Type I ◽

Mesenchymal Transition ◽

Fibrotic Process

Diabetes-associated complications, such as retinopathy, nephropathy, cardiomyopathy, and atherosclerosis, the main consequences of long-term hyperglycemia, often lead to organ dysfunction, disability, and increased mortality. A common denominator of these complications is the myofibroblast-driven excessive deposition of extracellular matrix proteins. Although fibroblast appears to be the primary source of myofibroblasts, other cells, including endothelial cells, can generate myofibroblasts through a process known as endothelial to mesenchymal transition (EndMT). During EndMT, endothelial cells lose their typical phenotype to acquire mesenchymal features, characterized by the development of invasive and migratory abilities as well as the expression of typical mesenchymal products such as α-smooth muscle actin and type I collagen. EndMT is involved in many chronic and fibrotic diseases and appears to be regulated by complex molecular mechanisms and different signaling pathways. Recent evidence suggests that small RNAs, in particular microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are crucial mediators of EndMT. Furthermore, EndMT and miRNAs are both affected by oxidative stress, another key player in the pathophysiology of diabetic fibrotic complications. In this review, we provide an overview of the primary redox signals underpinning the diabetic-associated fibrotic process. Then, we discuss the current knowledge on the role of small RNAs in the regulation of EndMT in diabetic retinopathy, nephropathy, cardiomyopathy, and atherosclerosis and highlight potential links between oxidative stress and the dyad small RNAs-EndMT in driving these pathological states.

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Far Infrared Technology (FIT) Therapy Patches, Protects from Inflammation, Oxidative Stress and Promotes Cellular Vitality

Current Pharmaceutical Design ◽

10.2174/1381612826666200427112023 ◽

2020 ◽

Vol 26 (34) ◽

pp. 4323-4329

Author(s):

Donatella Pastore ◽

Francesca Pacifici ◽

Giampaolo Ciao ◽

Valentina Bedin ◽

Guido Pasquantonio ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Adhesion Molecule ◽

Molecular Mechanisms ◽

Far Infrared ◽

Hek 293 ◽

Markers Of Inflammation ◽

Therapeutic Benefits ◽

Tnf Α ◽

Infrared Technology

Background: It is known from the most recent literature that far-infrared (FIR) radiations promote a broad spectrum of therapeutic benefits for cells and tissues. Objective: To identify molecular mechanisms by which FIT patches, as a far infrared technology, protects against damage caused by inflammatory process and oxidative stress. Methods: Endothelial cells (HUVEC, Human Umbilical Vein Endothelial Cells) were used as in vitro experimental model. HUVEC were stimulated with a pro-inflammatory cytokine, TNF-α, or hydrogen peroxide (H2O2) to induce oxidative stress. As markers of inflammation were evaluated: VCAM1 (Vascular Cell Adhesion Molecule 1), ICAM1 (Intercellular Adhesion Molecule 1) and E-Selectin by Western Blot analysis. Oxidative stress was assessed by cytofluorimetric analysis. The experiments were performed on control cells (no patch) or in cells treated with the FIT infrared technology applied on the basis of the culture plate. Results: HUVEC stimulated with TNF-α and treated with FIT patches had significant reduction of the expression of VCAM1, ICAM1 and E-Selectin (p<0.05). HUVEC stimulated with H2O2 and treated with FIT patches were significantly protected from oxidative stress (p <0.01) when compared to control cells. We measured cell viability and proliferation in HUVEC and HEK-293 (Human embryonic kidney cells) cells by MTT assay. HEK-293 and HUVEC treated with FIT patches showed a significantly higher percentage of basal vitality compared to control cells (p<0.0001 for HEK-293, p<0.05 for HUVEC). Conclusion: FIT therapy patches - infrared technology, through these protective mechanisms, could be used in all pathologies where an increase in inflammation, oxidative stress and degenerative state are present.

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Cytoprotective Peptides from Blue Mussel Protein Hydrolysates: Identification and Mechanism Investigation in Human Umbilical Vein Endothelial Cells Injury

Marine Drugs ◽

10.3390/md19110609 ◽

2021 ◽

Vol 19 (11) ◽

pp. 609

Author(s):

Indyaswan Tegar Suryaningtyas ◽

Chang-Bum Ahn ◽

Jae-Young Je

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Molecular Mechanisms ◽

Blue Mussel ◽

Umbilical Vein ◽

Ros Generation ◽

Heme Oxygenase 1 ◽

Human Umbilical Vein ◽

Bax Protein ◽

Umbilical Vein Endothelial Cells

Cardiovascular disease represents a leading cause of mortality and is often characterized by the emergence of endothelial dysfunction (ED), a physiologic condition that takes place in the early progress of atherosclerosis. In this study, two cytoprotective peptides derived from blue mussel chymotrypsin hydrolysates with the sequence of EPTF and FTVN were purified and identified. Molecular mechanisms underlying the cytoprotective effects against oxidative stress which lead to human umbilical vein endothelial cells (HUVEC) injury were investigated. The results showed that pretreatment of EPTF, FTVN and their combination (1:1) in 0.1 mg/mL significantly reduced HUVEC death due to H2O2 exposure. The cytoprotective mechanism of these peptides involves an improvement in the cellular antioxidant defense system, as indicated by the suppression of the intracellular ROS generation through upregulation of the cytoprotective enzyme heme oxygenase-1. In addition, H2O2 exposure triggers HUVEC damage through the apoptosis process, as evidenced by increased cytochrome C release, Bax protein expression, and the elevated amount of activated caspase-3, however in HUVEC pretreated with peptides and their combination, the presence of those apoptotic stimuli was significantly decreased. Each peptide showed similar cytoprotective effect but no synergistic effect. Taken together, these peptides may be especially important in protecting against oxidative stress-mediated ED.

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Hsa_circ_0004831 downregulation is partially responsible for atorvastatinalleviated human umbilical vein endothelial cell injuries induced by ox-LDL through targeting the miR-182-5p/CXCL12 axis

BMC Cardiovascular Disorders ◽

10.1186/s12872-021-01998-4 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Gang Su ◽

Guangli Sun ◽

Jian Lv ◽

Weiwei Zhang ◽

Hai Liu ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Endothelial Cell ◽

Cell Viability ◽

Molecular Mechanisms ◽

Inflammatory Responses ◽

Umbilical Vein ◽

Luciferase Reporter ◽

Cycle Progression ◽

Human Umbilical Vein

Abstract Background The dysfunction and injury of human umbilical vein endothelial cells (HUVECs) are key events of atherosclerosis (AS). Atorvastatin (ATV) has been shown to play a protective role on endothelial cells. However, the associated molecular mechanisms remain not fully illustrated. Methods HUVECs were treated with oxidized low-density lipoprotein (ox-LDL) to mimic the pathological conditions of endothelial cell injury in AS. Cell injuries were assessed according to cell viability, cell apoptosis, cycle progression, oxidative stress and inflammatory responses using CCK-8 assay, flow cytometry assay or commercial kits. The expression of hsa_circ_0004831, miR-182-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was examined using quantitative real-time PCR (qPCR). The expression of CXCL12 protein was quantitated by western blot. The predicted target relationship between miR-182-5p and hsa_circ_0004831 or CXCL12 was verified by pull-down assay, dual-luciferase reporter assay or RIP assay. Results The expression of hsa_circ_0004831 was upregulated by ox-LDL but downregulated by ATV in HUVECs. ATV promoted cell viability and cell cycle progression but inhibited apoptosis, oxidative stress and inflammation in ox-LDL-treated HUVECs, while the role of ATV was partially reversed by hsa_circ_0004831 overexpression. MiR-182-5p was targeted by hsa_circ_0004831, and hsa_circ_0004831 overexpression-restored apoptosis, oxidative stress and inflammation were blocked by miR-182-5p restoration. Further, CXCL12 was targeted by miR-182-5p, and miR-182-5p inhibition-stimulated apoptosis, oxidative stress and inflammation were lessened by CXCL12 knockdown. Conclusion Hsa_circ_0004831-targeted miR-182-5p/CXCL12 regulatory network is one of the pathways by which ATV protects against ox-LDL-induced endothelial injuries.

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