Differences between common endothelial cell models (primary human aortic endothelial cells and EA.hy926 cells) revealed through transcriptomics, bioinformatics, and functional analysis

Wang, Dongdong; Zhu, Chen; Yeung, Andy Wai Kan; Atanasov, Atanas G.

doi:10.1016/j.crbiot.2021.05.001

Cited by 6 publications

(4 citation statements)

References 42 publications

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“…Although the exact reason for this variation is unknown, it could be due to the difference in the spike protein treatment time and/or the cells used for the ACE2 expression analysis. A recent study identified differences, particularly in endothelial permeability, between EA.hy296 cells and primary human aortic ECs [ 61 ]. Although the use of EA.hy296 cells is a limitation of this study, most of the results we obtained for the S1 protein-induced EC permeability using EA.hy296 cells matched that obtained by using primary microvascular ECs (MVECs) by others [ 28 , 29 ].…”

Section: Discussionmentioning

confidence: 99%

Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion

Guo

Kanamarlapudi

2023

IJMS

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Coronavirus disease COVID-19, which is caused by severe acute respiratory syndrome coronavirus SARS-CoV-2, has become a worldwide pandemic in recent years. In addition to being a respiratory disease, COVID-19 is a ‘vascular disease’ since it causes a leaky vascular barrier and increases blood clotting by elevating von Willebrand factor (vWF) levels in the blood. In this study, we analyzed in vitro how the SARS-CoV-2 spike protein S1 induces endothelial cell (EC) permeability and its vWF secretion, and the underlying molecular mechanism for it. We showed that the SARS-CoV-2 spike protein S1 receptor-binding domain (RBD) is sufficient to induce endothelial permeability and vWF-secretion through the angiotensin-converting enzyme (ACE)2 in an ADP-ribosylation factor (ARF)6 activation-dependent manner. However, the mutants, including those in South African and South Californian variants of SARS-CoV-2, in the spike protein did not affect its induced EC permeability and vWF secretion. In addition, we have identified a signaling cascade downstream of ACE2 for the SARS-CoV-2 spike protein-induced EC permeability and its vWF secretion by using pharmacological inhibitors. The knowledge gained from this study could be useful in developing novel drugs or repurposing existing drugs for treating infections of SARS-CoV-2, particularly those strains that respond poorly to the existing vaccines.

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Section: Discussionmentioning

confidence: 99%

Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion

Guo

Kanamarlapudi

2023

IJMS

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“…A limitation of our study is that EA.hy926 cells are derived from the fusion of human umbilical vein endothelial cells (HUVEC) with A549 lung cancer cells however, they mostly retain endothelial characteristics and are widely used in in vitro endothelial cell models. [44][45][46][47][48]…”

Section: Discussionmentioning

confidence: 99%

“…Although it would be very intriguing to assess the effects of the above PDF in our in vitro system, these solutions are not yet commercially available. A limitation of our study is that EA.hy926 cells are derived from the fusion of human umbilical vein endothelial cells (HUVEC) with A549 lung cancer cells however, they mostly retain endothelial characteristics and are widely used in in vitro endothelial cell models 44–48 …”

Section: Discussionmentioning

confidence: 99%

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes

Jagirdar,

Pitaraki,

Rouka

et al. 2023

Artificial Organs

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IntroductionPeritoneal dialysis (PD) is a life maintaining treatment in patients with end‐stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described.Materials and MethodsMesothelial (MeT‐5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin‐based, amino acid‐based, and glucose‐based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed.ResultsCell proliferation and cell‐mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected.ConclusionsIn 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

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“…However, due to their hybrid nature, EA.hy926 cells may have some different characteristics compared to primary ECs. Indeed, a recent study demonstrated that EA.hy926 cells are deficient in some endothelial properties and have a transcriptomic profile that differs from primary ECs [20]. In the current study, we first established a comparative characterization of DOX-induced senescence phenotypes across EA.hy926 cells and HUVECs and then compared the senolytic effects of multiple senolytics in both cell lines.…”

Section: Introductionmentioning

confidence: 94%

EA.hy926 Cells and HUVECs Share Similar Senescence Phenotypes but Respond Differently to the Senolytic Drug ABT-263

Abdelgawad

Agostinucci

Ismail

et al. 2022

Cells

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Doxorubicin (DOX) induces endothelial cell (EC) senescence, which contributes to endothelial dysfunction and cardiovascular complications. Senolytic drugs selectively eliminate senescent cells to ameliorate senescence-mediated pathologies. Previous studies have demonstrated differences between immortalized and primary EC models in some characteristics. However, the response of DOX-induced senescent ECs to senolytics has not been determined across these two models. In the present work, we first established a comparative characterization of DOX-induced senescence phenotypes in immortalized EA.hy926 endothelial-derived cells and primary human umbilical vein EC (HUVECs). Thereafter, we evaluated the senolytic activity of four senolytics across both ECs. Following the DOX treatment, both EA.hy926 and HUVECs shared similar senescence phenotypes characterized by upregulated senescence markers, increased SA-β-gal activity, cell cycle arrest, and elevated expression of the senescence-associated secretory phenotype (SASP). The potentially senolytic drugs dasatinib, quercetin, and fisetin demonstrated a lack of selectivity against DOX-induced senescent EA.hy926 cells and HUVECs. However, ABT-263 (Navitoclax) selectively induced the apoptosis of DOX-induced senescent HUVECs but not EA.hy926 cells. Mechanistically, DOX-treated EA.hy926 cells and HUVECs demonstrated differential expression levels of the BCL-2 family proteins. In conclusion, both EA.hy926 cells and HUVECs demonstrate similar DOX-induced senescence phenotypes but they respond differently to ABT-263, presumably due to the different expression levels of BCL-2 family proteins.

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Differences between common endothelial cell models (primary human aortic endothelial cells and EA.hy926 cells) revealed through transcriptomics, bioinformatics, and functional analysis

Cited by 6 publications

References 42 publications

Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion

Molecular Analysis of SARS-CoV-2 Spike Protein-Induced Endothelial Cell Permeability and vWF Secretion

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes

EA.hy926 Cells and HUVECs Share Similar Senescence Phenotypes but Respond Differently to the Senolytic Drug ABT-263

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