Endothelial dysfunction contributes to severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

AbstractThe systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 in acute disease (n = 58) and in disease recovery in convalescent patients (n = 28) from Hannover Medical School, we used flow cytometry and proteomics data with unsupervised clustering analyses. In our observational study, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but the expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. The core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

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Endothelial dysfunction determines severe COVID-19 in combination with dysregulated lymphocyte responses and cytokine networks

10.1101/2021.07.08.21260169 ◽

2021 ◽

Author(s):

Louisa Ruhl ◽

Isabell Pink ◽

Jenny F Kuehne ◽

Kerstin Beushausen ◽

Jana Keil ◽

...

Keyword(s):

Immune Responses ◽

Plasma Proteins ◽

Endothelial Activation ◽

Inflammatory Microenvironment ◽

Life Threatening ◽

Strong Inflammatory Response ◽

Disease Recovery ◽

Cytokine Networks ◽

Endothelial Integrity ◽

Lymphocyte Responses

The systemic processes involved in the manifestation of life-threatening COVID-19 and in disease recovery are still incompletely understood, despite investigations focusing on the dysregulation of immune responses after SARS-CoV-2 infection. To define hallmarks of severe COVID-19 and disease recovery in convalescent patients, we combined analyses of immune cells and cytokine/chemokine networks with endothelial activation and injury. ICU patients displayed an altered immune signature with prolonged lymphopenia but expansion of granulocytes and plasmablasts along with activated and terminally differentiated T and NK cells and high levels of SARS-CoV-2-specific antibodies. Core signature of seven plasma proteins revealed a highly inflammatory microenvironment in addition to endothelial injury in severe COVID-19. Changes within this signature were associated with either disease progression or recovery. In summary, our data suggest that besides a strong inflammatory response, severe COVID-19 is driven by endothelial activation and barrier disruption, whereby recovery depends on the regeneration of the endothelial integrity.

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Abstract: P249 LOSS OF ENDOTHELIAL INTEGRITY AND ENDOTHELIAL ACTIVATION PRECEDE INTIMAL HYPERPLASIA IN SURGICALLY TRANSFERRED VENOUS GRAFTS IN MICE

Atherosclerosis Supplements ◽

10.1016/s1567-5688(09)70544-6 ◽

2009 ◽

Vol 10 (2) ◽

pp. e556

Author(s):

C-N Tseng ◽

E Karlöf ◽

U Hedin ◽

E Eriksson

Keyword(s):

Intimal Hyperplasia ◽

Endothelial Activation ◽

Venous Grafts ◽

Endothelial Integrity

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Inflammatory Cytokines in Cancer: Comprehensive Understanding and Clinical Progress in Gene Therapy

Cells ◽

10.3390/cells10010100 ◽

2021 ◽

Vol 10 (1) ◽

pp. 100

Author(s):

Tianxia Lan ◽

Li Chen ◽

Xiawei Wei

Keyword(s):

Gene Therapy ◽

Inflammatory Cytokines ◽

Gene Editing ◽

Considerable Effort ◽

Inflammatory Microenvironment ◽

Gene Therapies ◽

Life Threatening ◽

New Gene ◽

The Relationship ◽

Shed Light

The relationship between chronic inflammation and neoplastic diseases is not fully understood. The inflammatory microenvironment of a tumor is an intricate network that consists of numerous types of cells, cytokines, enzymes and signaling pathways. Recent evidence shows that the crucial components of cancer-related inflammation are involved in a coordinated system to influence the development of cancer, which may shed light on the development of potential anticancer therapies. Since the last century, considerable effort has been devoted to developing gene therapies for life-threatening diseases. When it comes to modulating the inflammatory microenvironment for cancer therapy, inflammatory cytokines are the most efficient targets. In this manuscript, we provide a comprehensive review of the relationship between inflammation and cancer development, especially focusing on inflammatory cytokines. We also summarize the clinical trials for gene therapy targeting inflammatory cytokines for cancer treatment. Future perspectives concerned with new gene-editing technology and novel gene delivery systems are finally provided.

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Endothelial dysfunction associated with obesity and the effect of weight loss interventions

Proceedings of The Nutrition Society ◽

10.1017/s0029665111001674 ◽

2011 ◽

Vol 70 (4) ◽

pp. 418-425 ◽

Cited By ~ 18

Author(s):

S. M. P. Kerr ◽

M. B. E. Livingstone ◽

T. A. McCrorie ◽

J. M. W. Wallace

Keyword(s):

Weight Loss ◽

Endothelial Function ◽

Vascular Endothelial Cells ◽

Endothelial Activation ◽

Endothelial Damage ◽

Convincing Evidence ◽

Fat Depots ◽

Increased Risk ◽

Potent Vasodilator ◽

Endothelial Integrity

Endothelial damage is central to the initiation and progression of atherosclerosis, while in addition vascular endothelial cells secrete several anti-atherogenic substances including the potent vasodilator nitric oxide. Increased adhesion molecule expression, in response to pathophysiological stimuli is perhaps the earliest indicator of compromised endothelial integrity. Obesity and adiposity are associated with an increased risk of CVD, influencing disease progression via a number of mechanisms, including enhanced endothelial activation. This review discusses possible mechanisms linking adiposity and more specifically regional fat depots with endothelial function and evaluates studies investigating the effect of weight loss on endothelial function, assessed by biochemical and physiological measurements. Overall, the research to date suggests that visceral adiposity is a stronger predictor of endothelial activation than overall adiposity, possibly mediated via the action of NEFA in circulation. While in general there is a suggestion that weight loss is associated with significant improvements in endothelial function, this is not apparent in all interventions and published literature to date provides less than convincing evidence for the effects of weight loss on endothelial activation.

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Endothelial Progenitor Cells and Rheumatoid Arthritis: Response to Endothelial Dysfunction and Clinical Evidences

International Journal of Molecular Sciences ◽

10.3390/ijms222413675 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13675

Author(s):

Klara Komici ◽

Angelica Perna ◽

Aldo Rocca ◽

Leonardo Bencivenga ◽

Giuseppe Rengo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Progenitor Cells ◽

Endothelial Progenitor Cells ◽

Endothelial Activation ◽

Endothelial Damage ◽

Current Evidence ◽

Endothelial Progenitor ◽

Cardiovascular Comorbidities ◽

And Function ◽

Endothelial Integrity

Rheumatoid Arthritis (RA) is a chronic autoimmune inflammatory disease characterized by the swelling of multiple joints, pain and stiffness, and accelerated atherosclerosis. Sustained immune response and chronic inflammation, which characterize RA, may induce endothelial activation, damage and dysfunction. An equilibrium between endothelial damage and repair, together with the preservation of endothelial integrity, is of crucial importance for the homeostasis of endothelium. Endothelial Progenitor Cells (EPCs) represent a heterogenous cell population, characterized by the ability to differentiate into mature endothelial cells (ECs), which contribute to vascular homeostasis, neovascularization and endothelial repair. A modification of the number and function of EPCs has been described in numerous chronic inflammatory and auto-immune conditions; however, reports that focus on the number and functions of EPCs in RA are characterized by conflicting results, and discrepancies exist among different studies. In the present review, the authors describe EPCs’ role and response to RA-related endothelial modification, with the aim of illustrating current evidence regarding the level of EPCs and their function in this disease, to summarize EPCs’ role as a biomarker in cardiovascular comorbidities related to RA, and finally, to discuss the modulation of EPCs secondary to RA therapy.

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Assembly of VP26 in herpes simplex virus-1 capsid implicated by 3-D structure of recombinant capsid

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100140579 ◽

1995 ◽

Vol 53 ◽

pp. 840-841

Author(s):

Z. Hong Zhou ◽

Jing He ◽

Joanita Jakana ◽

J. D. Tatman ◽

Frazer J. Rixon ◽

...

Keyword(s):

Herpes Simplex Virus ◽

Herpes Simplex ◽

3D Structure ◽

Structure Study ◽

Herpes Simplex Virus 1 ◽

Shell Proteins ◽

Life Threatening ◽

Infected Cells ◽

Simplex Virus ◽

Hsv 1

Herpes simplex virus-1 (HSV-1) is a ubiquitous virus which is implicated in diseases ranging from self-curing cold sores to life-threatening infections. The 2500 Å diameter herpes virion is composed of a glycoprotein spike containing, lipid envelope, enclosing a protein layer (the tegument) in which is embedded the capsid (which contains the dsDNA genome). The B-, and A- and C-capsids, representing different morphogenetic stages in HSV-1 infected cells, are composed of 7, and 5 structural proteins respectively. The three capsid types are organized in similar T=16 icosahedral shells with 12 pentons, 150 hexons, and 320 connecting triplexes. Our previous 3D structure study at 26 Å revealed domain features of all these structural components and suggested probable locations for the outer shell proteins, VP5, VP26, VP19c and VP23. VP5 makes up most of both pentons and hexons. VP26 appeared to bind to the VP5 subunit in hexon but not to that in penton.

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Processing Metabolomics and Proteomics Data with Open Software

10.1039/9781788019880 ◽

2020 ◽

Keyword(s):

Proteomics Data

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An Overview of Dementias

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd21.3.75 ◽

2012 ◽

Vol 21 (3) ◽

pp. 75-84

Author(s):

Venkata Vijaya K. Dalai ◽

Jason E. Childress ◽

Paul E Schulz

Keyword(s):

Clinical Presentation ◽

Treatment Options ◽

Current Treatment ◽

Great Variability ◽

Health Concern ◽

Public Health Concern ◽

Life Threatening ◽

The Common ◽

Neurodegenerative Dementias ◽

Made In

Dementia is a major public health concern that afflicts an estimated 24.3 million people worldwide. Great strides are being made in order to better diagnose, prevent, and treat these disorders. Dementia is associated with multiple complications, some of which can be life-threatening, such as dysphagia. There is great variability between dementias in terms of when dysphagia and other swallowing disorders occur. In order to prepare the reader for the other articles in this publication discussing swallowing issues in depth, the authors of this article will provide a brief overview of the prevalence, risk factors, pathogenesis, clinical presentation, diagnosis, current treatment options, and implications for eating for the common forms of neurodegenerative dementias.

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