scholarly journals SARS-CoV-2 Infection Remodels the Phenotype and Promotes Angiogenesis of Primary Human Lung Endothelial Cells

2021 ◽  
Vol 9 (7) ◽  
pp. 1438
Author(s):  
Francesca Caccuri ◽  
Antonella Bugatti ◽  
Alberto Zani ◽  
Antonella De Palma ◽  
Dario Di Silvestre ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Dysfunction ◽  
Proteome Analysis ◽  
Immunofluorescence Assay ◽  
Direct Role ◽  
Intussusceptive Angiogenesis ◽  
Cytopathic Effects ◽  
Life Threatening ◽  
Lung Endothelial Cells

SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) and acute lung injury are life-threatening manifestations of severe viral infection. The pathogenic mechanisms that lead to respiratory complications, such as endothelialitis, intussusceptive angiogenesis, and vascular leakage remain unclear. In this study, by using an immunofluorescence assay and in situ RNA-hybridization, we demonstrate the capability of SARS-CoV-2 to infect human primary lung microvascular endothelial cells (HL-mECs) in the absence of cytopathic effects and release of infectious particles. Preliminary data point to the role of integrins in SARS-CoV-2 entry into HL-mECs in the absence of detectable ACE2 expression. Following infection, HL-mECs were found to release a plethora of pro-inflammatory and pro-angiogenic molecules, as assessed by microarray analyses. This conditioned microenvironment stimulated HL-mECs to acquire an angiogenic phenotype. Proteome analysis confirmed a remodeling of SARS-CoV-2-infected HL-mECs to inflammatory and angiogenic responses and highlighted the expression of antiviral molecules as annexin A6 and MX1. These results support the hypothesis of a direct role of SARS-CoV-2-infected HL-mECs in sustaining vascular dysfunction during the early phases of infection. The construction of virus-host interactomes will be instrumental to identify potential therapeutic targets for COVID-19 aimed to inhibit HL-mEC-sustained inflammation and angiogenesis upon SARS-CoV-2 infection.

Abstract TP99: Human Lung Endothelial Cell Anti-Inflammatory and Regenerative Responses in Acute Ischemic Stroke

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Nikunj Satani ◽  
Kaavya Giridhar ◽  
Natalia Wewior ◽  
Dominique D Norris ◽  
Scott D Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Inflammatory Factors ◽  
Stroke Severity ◽  
Stroke Patients ◽  
Anti Inflammatory ◽  
Lung Endothelial Cells ◽  
Stroke Mimic

Background: Inflammatory responses after stroke consists of central and peripheral immune responses. The role of the spleen after stroke is well-known, however the role of the lungs has not been studied in detail. We explored the relation between stroke severity and immunomodulatory changes in lung endothelial cells. Methods: Human pulmonary endothelial cells (hPECs, Cell Biologics) were cultured at passage 3. Serum from stroke patients with NIH Stroke Scale (NIHSS) severity ranging from 0 to 20 was collected at 24 hours after stroke. hPECs were exposed to media with 1) 10% FBS alone (N=6), 2) 10% serum from stroke patients (N=72), or 3) 10% serum from stroke mimic patients (N=6). After 3 hour of exposure, fresh media was added and secretomes from hPECs were measured after 24 hours. We isolated RNA from hPECs after 3 hour of serum exposure and measured gene expression (N=6 for each group). Secretome and gene changes in hPECs were analyzed based on stroke severity, tPA treatment, and co-morbidities. Results: Serum from stroke patients reduced the secretion of IL-8, MCP-1 and Fractalkine (p<0.01), and increased the secretion of VEGF and BDNF (p<0.01) from hPECs. These effects were more pronounced depending on stroke severity (Fig). There was no effect of tPA or T2DM on hPECs secretomes. There was significantly reduced gene expression of IL-6, IL-8, MCP-1 and IL-1β and significantly higher expression of ICAM1, IGF-1 and TGF-β1 as compared to stroke mimics. Conclusion: Exposure of hPECs to serum from stroke patients alters their immunomodulatory properties. Higher severity of stroke leads to more protective response from hPECs by reducing the secretion of pro-inflammatory factors, while increasing the secretion of anti-inflammatory factors.

scholarly journals Enhanced circulating levels of CD3 cells-derived extracellular vesicles in different forms of pulmonary hypertension

2019 ◽  
Vol 9 (3) ◽  
pp. 204589401986435 ◽  
Author(s):  
Djuro Kosanovic ◽  
Ujjwal Deo ◽  
Henning Gall ◽  
Balachandar Selvakumar ◽  
Susanne Herold ◽  
...  
Keyword(s):  
T Cells ◽  
Endothelial Cells ◽  
Pulmonary Hypertension ◽  
Extracellular Vesicles ◽  
Inflammatory Cells ◽  
Circulating Endothelial Cells ◽  
Profound Knowledge ◽  
Life Threatening ◽  
Circulating Levels

It has been shown previously that increased circulating endothelial cells-derived extracellular vesicles represent an important pathological attribute of pulmonary hypertension. Although it is a well-known fact that inflammatory cells may also release extracellular vesicles, and pulmonary hypertension is a disease associated with abnormal inflammation, there is no profound knowledge with regard to the role of inflammatory cells-derived extracellular vesicles. Therefore, our study demonstrated that circulating levels of extracellular vesicles derived from T-cells are enhanced in various pulmonary hypertension forms and that endothelial cells-derived extracellular vesicles may have distinctive profiles in different clinical subgroups of pulmonary hypertension, which still remains as a poorly treatable and life-threatening disorder.

scholarly journals Role of Nox4 and Nox2 in Hyperoxia-Induced Reactive Oxygen Species Generation and Migration of Human Lung Endothelial Cells

2009 ◽  
Vol 11 (4) ◽  
pp. 747-764 ◽  
Author(s):  
Srikanth Pendyala ◽  
Irina A Gorshkova ◽  
Peter V. Usatyuk ◽  
Donghong He ◽  
Arjun Pennathur ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Endothelial Cells ◽  
Human Lung ◽  
Reactive Oxygen Species Generation ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Lung Endothelial Cells ◽  
And Migration

Nitric oxide upregulation of caspase-8 mRNA expression in lung endothelial cells: role of JAK2/STAT-1 signaling

2007 ◽  
Vol 305 (1-2) ◽  
pp. 71-77 ◽  
Author(s):  
Liuzhe Li ◽  
Jianliang Zhang ◽  
Bilian Jin ◽  
Edward R. Block ◽  
Jawaharlal M. Patel
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Mrna Expression ◽  
Caspase 8 ◽  
Lung Endothelial Cells

The role of cholesteryl ester transfer protein expression on endothelial cells: oxidative stress and vascular dysfunction

2017 ◽  
Vol 108 ◽  
pp. S96
Author(s):  
Amarylis Claudine Bonito Wanschel ◽  
Estela Lorza-Gil ◽  
Alessandro G. Salerno ◽  
Adriene A. Paiva ◽  
Jeferson Stravinsky ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Protein Expression ◽  
Cholesteryl Ester ◽  
Cholesteryl Ester Transfer Protein ◽  
Vascular Dysfunction ◽  
Transfer Protein

scholarly journals Fucosylated Chondroitin Sulfate Inhibits Plasmodium falciparum Cytoadhesion and Merozoite Invasion

2014 ◽  
Vol 58 (4) ◽  
pp. 1862-1871 ◽  
Author(s):  
Marcele F. Bastos ◽  
Letusa Albrecht ◽  
Eliene O. Kozlowski ◽  
Stefanie C. P. Lopes ◽  
Yara C. Blanco ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Plasmodium Falciparum ◽  
Chondroitin Sulfate ◽  
Parasite Development ◽  
Flow Conditions ◽  
Inhibitory Effects ◽  
Merozoite Invasion ◽  
Content Type ◽  
Life Threatening ◽  
Lung Endothelial Cells

ABSTRACTSequestration ofPlasmodium falciparum-infected erythrocytes (Pf-iEs) in the microvasculature of vital organs plays a key role in the pathogenesis of life-threatening malaria complications, such as cerebral malaria and malaria in pregnancy. This phenomenon is marked by the cytoadhesion of Pf-iEs to host receptors on the surfaces of endothelial cells, on noninfected erythrocytes, and in the placental trophoblast; therefore, these sites are potential targets for antiadhesion therapies. In this context, glycosaminoglycans (GAGs), including heparin, have shown the ability to inhibit Pf-iE cytoadherence and growth. Nevertheless, the use of heparin was discontinued due to serious side effects, such as bleeding. Other GAG-based therapies were hampered due to the potential risk of contamination with prions and viruses, as some GAGs are isolated from mammals. In this context, we investigated the effects and mechanism of action of fucosylated chondroitin sulfate (FucCS), a unique and highly sulfated GAG isolated from the sea cucumber, with respect toP. falciparumcytoadhesion and development. FucCS was effective in inhibiting the cytoadherence of Pf-iEs to human lung endothelial cells and placenta cryosections under static and flow conditions. Removal of the sulfated fucose branches of the FucCS structure virtually abolished the inhibitory effects of FucCS. Importantly, FucCS rapidly disrupted rosettes at high levels, and it was also able to block parasite development by interfering with merozoite invasion. Collectively, these findings highlight the potential of FucCS as a candidate for adjunct therapy against severe malaria.

scholarly journals Cross-linking of IgGs bound on circulating neutrophils leads to an activation of endothelial cells: possible role of rheumatoid factors in rheumatoid arthritis-associated vascular dysfunction

2013 ◽  
Vol 10 (1) ◽  
pp. 27 ◽  
Author(s):  
Emmanuelle Rollet-Labelle ◽  
Myriam Vaillancourt ◽  
Louis Marois ◽  
Marianna M Newkirk ◽  
Patrice E Poubelle ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Endothelial Cells ◽  
Vascular Dysfunction ◽  
Cross Linking ◽  
Rheumatoid Factors

scholarly journals Role of the CYP4A/20-HETE pathway in vascular dysfunction of the Dahl salt-sensitive rat

2013 ◽  
Vol 124 (12) ◽  
pp. 695-700 ◽  
Author(s):  
Kathleen M. Lukaszewicz ◽  
Julian H. Lombard
Keyword(s):  
Animal Model ◽  
Vascular Function ◽  
Genetic Model ◽  
Vascular Dysfunction ◽  
Human Subjects ◽  
Brown Norway ◽  
Direct Role ◽  
Norway Rat ◽  
Cytochrome P450 4A

20-HETE (20-hydroxyeicosatetraenoic acid), a vasoconstrictor metabolite of arachidonic acid formed through the action of CYP4A (cytochrome P450-4A) in vascular smooth muscle cells, has been implicated in the development of hypertension and vascular dysfunction. There have been a number of reports in human subjects demonstrating an association between elevated urinary excretion of 20-HETE and hypertension, as well as increased 20-HETE production and vascular dysfunction. The Dahl SS (salt-sensitive) rat is a genetic model of salt-sensitive hypertension that exhibits vascular dysfunction, even when maintained on a normal-salt diet and before the development of hypertension. This mini-review highlights our current research on the role of CYP4A and 20-HETE in the vascular dysfunction of the Dahl SS rat. In our studies, the SS rat is compared with the consomic SS-5BN rat, having chromosome 5 from the salt-resistant Brown Norway rat (carrying all CYP4A genes) introgressed on to the SS genetic background. Our laboratory has demonstrated restoration of normal vascular function in the SS rat with inhibition of the CYP4A/20-HETE pathway, suggesting a direct role for this pathway in the vascular dysfunction in this animal model. Our studies have also shown that the SS rat has an up-regulated CYP4A/20-HETE pathway within their cerebral vasculature compared with the SS-5BN consomic rat, which causes endothelial dysfunction through the production of ROS (reactive oxygen species). Our data shows that ROS influences the expression of the CYP4A/20-HETE pathway in the SS rat in a feed-forward mechanism whereby elevated ROS stimulates production of 20-HETE. The presence of this vicious cycle offers a possible explanation for the spiralling effects of elevated 20-HETE on the development of vascular dysfunction in this animal model.

Abstract 289: Non-viral Rna Delivery To The Endothelium

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
daniel anderson
Keyword(s):  
Endothelial Cells ◽  
Vascular Dysfunction ◽  
High Specificity ◽  
Cell Types ◽  
Small Interfering Rnas ◽  
Efficient Delivery ◽  
Tumor Growth And Metastasis ◽  
Reduce Gene Expression

Dysfunctional vasculature contributes to more disease than any other tissue in the body1. Small interfering RNAs (siRNAs) have the potential to help elucidate the role of endothelial cells in vivo by durably silencing multiple genes simultaneously, but this requires efficient delivery, which has remained challenging in cell types besides hepatocytes. We have developed nanoparticles that deliver siRNA to endothelial cells with high specificity, thereby facilitating the silencing of multiple endothelial cell genes in vivo. These particles do not significantly reduce gene expression in hepatocytes or immune cells even at doses forty times greater than those required for endothelial gene silencing. Optimized formulations achieved the most durable non-liver silencing reported to date, and delivered siRNAs that modified endothelial function in mouse models of vascular permeability, emphysema, primary tumor growth, and metastasis. We believe the nanomaterial described here may improve the ability to study endothelial gene function in vivo, and be used to treat diseases caused by vascular dysfunction.

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