ER-Stress and Senescence Coordinately Promote Endothelial Barrier Dysfunction in Diabetes-Induced Atherosclerosis
Abstract
:1. Introduction
2. Materials and Methods:
2.1. Reagents
2.2. Mice
2.3. Atherosclerotic Mouse Models
2.4. Cell Culture
2.5. Immunofluorescence Staining
2.6. Senescence-Associated Beta Galactosidase Staining
2.7. Immunoblotting
2.8. Fluorescein Isothiocyanate (FITC)-Dextran Vascular Endothelial Cells Permeability Assay
2.9. Transendothelial Electrical Resistance (TEER) Assay
2.10. Statistical Analysis
3. Results
3.1. High Glucose-Induced Senescence Promotes Barrier Disruption in Vascular Endothelial Cells
3.2. High Glucose Mediated Maladaptive UPR Signalling Impairs Vascular Endothelial Barrier Integrity
3.3. Activated Protein C Restricts the UPR and Prevents High Glucose-Induced Senescence in HCAECs
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Acknowledgments
Conflicts of Interest
Abbreviations
aPC | activated protein C |
ApoE | apolipoprotein E |
ASCVD | atherosclerotic cardiovascular disease |
ANOVA | analysis of variance |
DM | diabetes mellitus |
DAPI | 4′,6-diamidino-2-phenylindole |
DEPC | diethyl pyrocarbonate |
EPCR | endothelial protein C receptor |
NF-κB | nuclear factor kappa-light-chain-enhancer of activated B cells |
qPCR | quantitative polymerase chain reaction |
ROS | reactive oxygen species |
RT-PCR | reverse transcriptase polymerase chain reaction |
SMC | smooth muscle cells |
α-SMC | alpha-smooth muscle actin |
SEM | standard error mean |
STZ | streptozotocin |
TM | thrombomodulin |
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Fatima, S.; Ambreen, S.; Mathew, A.; Elwakiel, A.; Gupta, A.; Singh, K.; Krishnan, S.; Rana, R.; Khawaja, H.; Gupta, D.; et al. ER-Stress and Senescence Coordinately Promote Endothelial Barrier Dysfunction in Diabetes-Induced Atherosclerosis. Nutrients 2022, 14, 2786. https://doi.org/10.3390/nu14142786
Fatima S, Ambreen S, Mathew A, Elwakiel A, Gupta A, Singh K, Krishnan S, Rana R, Khawaja H, Gupta D, et al. ER-Stress and Senescence Coordinately Promote Endothelial Barrier Dysfunction in Diabetes-Induced Atherosclerosis. Nutrients. 2022; 14(14):2786. https://doi.org/10.3390/nu14142786
Chicago/Turabian StyleFatima, Sameen, Saira Ambreen, Akash Mathew, Ahmed Elwakiel, Anubhuti Gupta, Kunal Singh, Shruthi Krishnan, Rajiv Rana, Hamzah Khawaja, Dheerendra Gupta, and et al. 2022. "ER-Stress and Senescence Coordinately Promote Endothelial Barrier Dysfunction in Diabetes-Induced Atherosclerosis" Nutrients 14, no. 14: 2786. https://doi.org/10.3390/nu14142786