Overexpression of microRNA‑155 alleviates palmitate‑induced vascular endothelial cell injury in human umbilical vein endothelial cells by negatively regulating the Wnt signaling pathway

Deep venous thrombosis (DVT) constitutes a great threat to health worldwide. Endothelial cell injury and dysfunction comprise the critical contributor for the development of DVT. However, the mechanism behind it remains poorly elucidated. The study is aimed at investigating the role of microRNA-122 (miR-122) and oxidative stress on DVT. The results showed that miR-122 overexpression dampened H2O2-evoked cytotoxic injury in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, suppressing cell apoptosis and oxidative stress injury. Notably, miR-122 overexpression attenuated provasoconstriction factor endothelin-1 (ET-1) expression in HUVECs exposed to H2O2 but enhanced the productions of vasodilatation factor Prostaglandin F1α (PGF1α). Moreover, inhibition of miR-122 had the opposite results. miR-122 could inhibit the expression of p53. Low expression of p53 could enhance the protection of miR-122 on HUVEC injury. This study highlights that miR-122 overexpression may restore H2O2-induced HUVEC injury by regulating the expression of p53.

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Blocking the REDD1/TXNIP axis ameliorates LPS-induced vascular endothelial cell injury through repressing oxidative stress and apoptosis

AJP Cell Physiology ◽

10.1152/ajpcell.00313.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. C104-C110 ◽

Cited By ~ 8

Author(s):

Xuhui Hou ◽

Songbai Yang ◽

Jian Yin

Keyword(s):

Oxidative Stress ◽

Endothelial Cell ◽

Cell Injury ◽

Umbilical Vein ◽

Vascular Endothelial Cell ◽

Reactive Oxygen Species Generation ◽

Vascular Endothelial ◽

Interacting Protein ◽

Endothelial Cell Injury ◽

Lactate Dehydrogenase Release

The aim of the present study was to investigate the potential role of regulated in development and DNA damage response 1 (REDD1) in LPS-induced vascular endothelial injury by using human umbilical vein endothelial cells (HUVECs). We observed that REDD1 expression was apparently elevated in HUVECs after exposure to LPS. Additionally, elimination of REDD1 strikingly attenuated the secretion of the proinflammatory cytokines TNF-α, IL-6, IL-1β, and monocyte chemotactic protein-1 and the endothelial cell adhesion markers ICAM-1 and VCAM-1 that was induced by LPS stimulation. Subsequently, knockdown of REDD1 augmented cell viability but ameliorated lactate dehydrogenase release in HUVECs stimulated with LPS. Meanwhile, depletion of REDD1 effectively restricted LPS-induced HUVEC apoptosis, as exemplified by reduced DNA fragmentation, and it also elevated antiapoptotic Bcl-2 protein, concomitant with reduced levels of proapoptotic proteins Bax and cleaved caspase-3. Furthermore, repression of REDD1 remarkably alleviated LPS-triggered intracellular reactive oxygen species generation accompanied by decreased malondialdehyde content and increased the activity of the endogenous antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase. Most important, depletion of REDD1 protected HUVECs against inflammation-mediated apoptosis and oxidative damage partly through thioredoxin-interacting protein (TXNIP). Collectively, these findings indicate that blocking the REDD1/TXNIP axis repressed the inflammation-mediated vascular injury process, which may be closely related to oxidative stress and apoptosis in HUVECs, implying that the REDD1/TXNIP axis may be a new target for preventing the endothelial cell injury process.

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Omentin-1 Ameliorated Free Fatty Acid-Induced Impairment in Proliferation, Migration, and Inflammatory States of HUVECs

Cardiology Research and Practice ◽

10.1155/2020/3054379 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Yubin Chen ◽

Fen Liu ◽

Fei Han ◽

Lizhi Lv ◽

Can-e Tang ◽

...

Keyword(s):

Endothelial Cells ◽

Fatty Acid ◽

Endothelial Cell ◽

Free Fatty Acid ◽

Cell Injury ◽

Umbilical Vein ◽

Quantitative Polymerase Chain Reaction ◽

Cell Counting ◽

Endothelial Cell Injury ◽

Umbilical Vein Endothelial Cells

Objectives. Endothelial cell injury is a critical pathological change during the development of atherosclerosis. Here, we explored the effect of omentin-1 on free fatty acid- (FFA-) induced endothelial cell injury. Methods. An FFA-induced endothelial cell injury model was established to investigate the role of omentin-1 in this process. Cell proliferation was analyzed with the Cell Counting Kit assay and flow cytometry. Scratch and transwell assays were used to evaluate cell migration. Factors secreted by endothelial cells after injury were detected by western blotting, reverse-transcription quantitative polymerase chain reaction, and cellular fluorescence assay. Results. Omentin-1 rescued the FFA-induced impaired proliferation and migration capabilities of human umbilical vein endothelial cells (HUVECs). It decreased the number of THP-1 cells attached to HUVECs in response to injury and inhibited the FFA-induced proinflammatory state of HUVECs. Conclusion. Omentin-1 could partly ameliorate FFA-induced endothelial cell injury.

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Proteome-Scale Profiling Reveals MAFG and MAFF as Two Novel Candidate Key Transcription Factors Involved in Palmitic acid Induced Umbilical Vein Endothelial Cells Apoptosis

10.21203/rs.3.rs-72835/v1 ◽

2020 ◽

Author(s):

Mangyuan Wang ◽

Fen Liu ◽

Binbin Fang ◽

Qiang Huo ◽

Yining Yang

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Cell Apoptosis ◽

Umbilical Vein ◽

Vascular Endothelial Cell ◽

P Value ◽

Vascular Endothelial ◽

Endothelial Cell Apoptosis ◽

Family Protein ◽

Umbilical Vein Endothelial Cells

Abstract Backgrounds: Vascular endothelial cell apoptosis is the first risk factor of atherosclerosis (AS), and it can be induced by high doses of glucose and palmitic acid (PA). The purpose of our study is to use a new generation of high-throughput transcription factors (TFs) detecting method to identify novel candidate key TFs involved in PA-induced vascular endothelial cell apoptosis.Methods: Human umbilical vein endothelial cells (HUVECs) were treated with 0µM PA (control group), 250µM PA (group 1), or 500µM PA (group 2). Candidate TFs among the three groups were determined by significant changes according to t-test, and pathway enrichment, western blot (WB) and RT-qPCR were then performed.Results: Fifty-one TFs showing with significant p value were identified, and 24 TFs with significant p value plus fold change > 2 and with dose-dependence were identified with 12 TFs biologically validated in former studies. Two of the remaining 12 novel TFs, v-maf musculoaponeurotic fibrosarcoma oncogene family protein G (MAFG) and v-maf musculoaponeurotic fibrosarcoma oncogene family protein F (MAFF), were matched to AS known signalling pathways and were validated by WB and RT-qPCR in our study.Conclusions: We identified MAFG and MAFF as novel candidate key TFs in vascular endothelial cell apoptosis, which is the key initial process of AS.

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miR-101-3p induces vascular endothelial cell dysfunction by targeting tet methylcytosine dioxygenase 2

Acta Biochimica et Biophysica Sinica ◽

10.1093/abbs/gmz154 ◽

2020 ◽

Vol 52 (2) ◽

pp. 180-191 ◽

Cited By ~ 3

Author(s):

Qiaoli Chen ◽

Xiaoye Li ◽

Lingjun Kong ◽

Qing Xu ◽

Zi Wang ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Vascular Endothelial Cells ◽

Umbilical Vein ◽

Vascular Endothelial Cell ◽

Nuclear Factor Κb ◽

Vascular Endothelial ◽

Ros Production ◽

Cell Dysfunction ◽

Umbilical Vein Endothelial Cells

Abstract Endothelial cell (EC) dysfunction represents an early key event in atherosclerosis. Recently, MicroRNAs have been demonstrated to regulate EC function. miR-101-3p has been discovered to regulate cell apoptosis and proliferation in cardiovascular diseases. Therefore, the aim of the current study was to clarify whether miR-101-3p regulates the dysfunction of vascular endothelial cells. In this study, the transfection of human umbilical vein endothelial cells (HUVECs) with miR-101-3p mimic induced reactive oxygen species (ROS) production, EC dysfunction, and activated nuclear factor-κB (NF-κB), whereas transfection with miR-101-3p inhibitor alleviated these events. The antioxidant N-acetylcysteine alleviated miR-101-3p-induced EC dysfunction. Moreover, we observed that miR-101-3p inhibited the expression of tet methylcytosine dioxygenase 2 (TET2) at the posttranscriptional level, resulting in increased ROS production and activated NF-κB. TET2 overexpression inhibited ROS production, EC dysfunction, and NF-κB activation in miR-101-3p-transfected HUVECs. These results indicate that miR-101-3p induces EC dysfunction by targeting TET2, which regulates ROS production, EC dysfunction, and NF-κB activation. Taken together, our current study reveals a novel pathway associated with EC dysfunction. The modulation of miR-101-3p and TET2 expression levels may serve as a potential target for therapeutic strategies for atherosclerosis.

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Fluidization, resolidification, and reorientation of the endothelial cell in response to slow tidal stretches

AJP Cell Physiology ◽

10.1152/ajpcell.00074.2012 ◽

2012 ◽

Vol 303 (4) ◽

pp. C368-C375 ◽

Cited By ~ 40

Author(s):

Ramaswamy Krishnan ◽

Elizabeth Peruski Canović ◽

Andreea L. Iordan ◽

Kavitha Rajendran ◽

Greeshma Manomohan ◽

...

Keyword(s):

Endothelial Cells ◽

Endothelial Cell ◽

Umbilical Vein ◽

Vascular Endothelial Cell ◽

Mechanical Stretch ◽

Vascular Endothelial ◽

Cell Mapping ◽

Traction Forces ◽

Morphological Response ◽

Umbilical Vein Endothelial Cells

Mechanical stretch plays an important role in regulating shape and orientation of the vascular endothelial cell. This morphological response to stretch is basic to angiogenesis, neovascularization, and vascular homeostasis, but mechanism remains unclear. To elucidate mechanisms, we used cell mapping rheometry to measure traction forces in primary human umbilical vein endothelial cells subjected to periodic uniaxial stretches. Onset of periodic stretch of 10% strain amplitude caused a fluidization response typified by attenuation of traction forces almost to zero. As periodic stretch continued, the prompt fluidization response was followed by a slow resolidification response typified by recovery of the traction forces, but now aligned along the axis perpendicular to the imposed stretch. Reorientation of the cell body lagged reorientation of the traction forces, however. Together, these observations demonstrate that cellular reorientation in response to periodic stretch is preceded by traction attenuation by means of cytoskeletal fluidization and subsequent traction recovery transverse to the stretch direction by means of cytoskeletal resolidification.

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