RhoA Signaling in Immune Cell Response and Cardiac Disease

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spiral down to immune cell activation and chronic state of low-level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

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RhoA Signaling in Immune Cell Response and Cardiac Disease

10.20944/preprints202106.0270.v1 ◽

2021 ◽

Author(s):

Lucia Sophie Kilian ◽

Derk Frank ◽

Ashraf Yusuf Rangrez

Keyword(s):

Cardiac Disease ◽

Cell Response ◽

Cell Activation ◽

Immune Cell ◽

Inflammatory Diseases ◽

Heart Diseases ◽

Small Gtpase ◽

Cardiac Inflammation ◽

Immune Cell Activation ◽

Immune Cell Response

Chronic inflammation, the activation of immune cells and their cross-talk with cardiomyocytes in the pathogenesis and progression of heart diseases has long been overlooked. However, with the latest research developments, it is increasingly accepted that a vicious cycle exists where cardiomyocytes release cardiocrine signaling molecules that spirals down to immune cell activation and chronic state of low‐level inflammation. For example, cardiocrine molecules released from injured or stressed cardiomyocytes can stimulate macrophages, dendritic cells, neutrophils and even T-cells, which then subsequently increase cardiac inflammation by co-stimulation and positive feedback-loops. One of the key proteins involved in stress-mediated cardiomyocyte signal transduction is a small GTPase RhoA. Importantly, the regulation of RhoA activation is critical for effective immune cell response and is being considered as one of the potential therapeutic targets in many immune-cell-mediated inflammatory diseases. In this review we provide an update on the role of RhoA at the juncture of immune cell activation, inflammation and cardiac disease.

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Prevention of NF-κB activation in vivo by a cell-permeable NF-κB inhibitor peptide

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.00164.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. L536-L544 ◽

Cited By ~ 16

Author(s):

Ana L. Mora ◽

John LaVoy ◽

Martha McKean ◽

Arlene Stecenko ◽

Kenneth L. Brigham ◽

...

Keyword(s):

Recombinant Protein ◽

Stress Responses ◽

Cell Activation ◽

Immune Cell ◽

Nuclear Translocation ◽

Inflammatory Diseases ◽

New Approach ◽

Immune Cell Activation ◽

A Cell

The NF-κB/Rel transcription factor family plays a central role in coordinating the expression of a variety of genes that regulate stress responses, immune cell activation, apoptosis, proliferation, differentiation, and oncogenic transformation. Interventions that target the NF-κB pathway may be therapeutic for a variety of pathologies, especially immune/inflammatory diseases. Using membrane translocating sequence (MTS) technology, we developed a cell-permeable dominant inhibitor of NF-κB activation, termed IκBα-(ΔN)-MTS. This molecule contains a 12-amino acid MTS motif attached to the COOH-terminal region of a nondegradable inhibitor protein [IκBα-(ΔN)]. The recombinant protein enters cells and localizes in the cytoplasm. Delivery of the IκBα-(ΔN)-MTS to cell lines and primary cells inhibited nuclear translocation of NF-κB proteins induced by cell activation. The protein also effectively inhibited NF-κB activation in vivo in two different animal models: NF-κB activation in response to skin wounding in mice and NF-κB activation in lungs after endotoxin treatment in sheep. Inhibition of NF-κB by the IκBα-(ΔN)-MTS in the endotoxin model attenuated physiological responses to endotoxemia. These data demonstrate that activation of NF-κB can be inhibited using a recombinant protein designed to penetrate into cells. This technology may provide a new approach to NF-κB pathway-targeted therapies.

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Oxidized Haemoglobin–Driven Endothelial Dysfunction and Immune Cell Activation: Novel Therapeutic Targets for Atherosclerosis

Current Medicinal Chemistry ◽

10.2174/09298673113209990162 ◽

2013 ◽

Vol 20 (37) ◽

pp. 4806-4814 ◽

Cited By ~ 8

Author(s):

Brigitta Buttari ◽

Elisabetta Profumo ◽

Rita Businaro ◽

Luciano Saso ◽

Raffaele Capoano ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Cell Activation ◽

Immune Cell ◽

Therapeutic Targets ◽

Immune Cell Activation ◽

Novel Therapeutic

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Neuronal guidance proteins in cardiovascular inflammation

Basic Research in Cardiology ◽

10.1007/s00395-021-00847-x ◽

2021 ◽

Vol 116 (1) ◽

Author(s):

Marius Keller ◽

Valbona Mirakaj ◽

Michael Koeppen ◽

Peter Rosenberger

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Vascular Endothelial ◽

Therapeutic Approaches ◽

Immune Cell Activation ◽

Cytokines And Chemokines ◽

The Future ◽

Cardiovascular Pathologies ◽

Neuronal Guidance

AbstractCardiovascular pathologies are often induced by inflammation. The associated changes in the inflammatory response influence vascular endothelial biology; they complicate the extent of ischaemia and reperfusion injury, direct the migration of immune competent cells and activate platelets. The initiation and progression of inflammation is regulated by the classical paradigm through the system of cytokines and chemokines. Therapeutic approaches have previously used this knowledge to control the extent of cardiovascular changes with varying degrees of success. Neuronal guidance proteins (NGPs) have emerged in recent years and have been shown to be significantly involved in the control of tissue inflammation and the mechanisms of immune cell activation. Therefore, proteins of this class might be used in the future as targets to control the extent of inflammation in the cardiovascular system. In this review, we describe the role of NGPs during cardiovascular inflammation and highlight potential therapeutic options that could be explored in the future.

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Oxidative stress and immune cell activation quantification in sepsis and non-sepsis critical care patients by neopterin/7,8-dihydroneopterin analysis

Pteridines ◽

10.1515/pteridines-2020-0015 ◽

2020 ◽

Vol 31 (1) ◽

pp. 68-82

Author(s):

Gregory Baxter-Parker ◽

Ravinder Reddy Gaddam ◽

Elena Moltchanova ◽

Anitra Carr ◽

Geoff Shaw ◽

...

Keyword(s):

Oxidative Stress ◽

Kidney Function ◽

Cell Activation ◽

Immune Cell ◽

Intensive Care Patients ◽

Immune Cell Activation ◽

Immune System Activation ◽

System Activation ◽

Urinary Neopterin ◽

Critical Care Patients

AbstractIntroduction: Neopterin and 7,8-dihydroneopterin are used as biomarkers of oxidative stress and inflammation, but the effect of kidney function on these measurements has not been extensively explored. We examine the levels of oxidative stress, inflammation and kidney function in intensive patients and compare them to equivalent patients without sepsis.Methods: 34 Intensive care patients were selected for the study, 14 without sepsis and 20 with. Both groups had equivalent levels of trauma, assessed by SAPS II, SOFA, and APACHE II and III scores. Plasma and urinary neopterin and total neopterin (neopterin + 7,8-dihydroneopterin) values were measured.Results: Neopterin and total neopterin were significantly elevated in urine and plasma for multiple days in sepsis versus non-sepsis patients. Plasma neopterin and total neopterin have decreasing relationships with increased eGFR (p<0.008 and p<0.001, respectively). Plasma/urinary neopterin and total neopterin ratios demonstrate that total neopterin flux is more influenced by eGFR than neopterin, with significantce of p<0.02 and p<0.0002 respectively.Conclusion: Sepsis patients present with greater levels of oxidative stress and immune system activation than non-sepsis patients of equal levels of trauma, as measured by neopterin and total neopterin. eGFR may need to be taken into account when accessing the level of inflammation from urinary neopterin measurements.

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Hybrid Nanoassemblies from Viruses and DNA Nanostructures

Nanomaterials ◽

10.3390/nano11061413 ◽

2021 ◽

Vol 11 (6) ◽

pp. 1413

Author(s):

Sofia Ojasalo ◽

Petteri Piskunen ◽

Boxuan Shen ◽

Mauri A. Kostiainen ◽

Veikko Linko

Keyword(s):

Cell Activation ◽

Immune Cell ◽

Dna Nanotechnology ◽

Biological Properties ◽

Dna Nanostructures ◽

Dna Structures ◽

Nanoscale Structures ◽

Immune Cell Activation ◽

Wide Range ◽

Structural Dna Nanotechnology

Viruses are among the most intriguing nanostructures found in nature. Their atomically precise shapes and unique biological properties, especially in protecting and transferring genetic information, have enabled a plethora of biomedical applications. On the other hand, structural DNA nanotechnology has recently emerged as a highly useful tool to create programmable nanoscale structures. They can be extended to user defined devices to exhibit a wide range of static, as well as dynamic functions. In this review, we feature the recent development of virus-DNA hybrid materials. Such structures exhibit the best features of both worlds by combining the biological properties of viruses with the highly controlled assembly properties of DNA. We present how the DNA shapes can act as “structured” genomic material and direct the formation of virus capsid proteins or be encapsulated inside symmetrical capsids. Tobacco mosaic virus-DNA hybrids are discussed as the examples of dynamic systems and directed formation of conjugates. Finally, we highlight virus-mimicking approaches based on lipid- and protein-coated DNA structures that may elicit enhanced stability, immunocompatibility and delivery properties. This development also paves the way for DNA-based vaccines as the programmable nano-objects can be used for controlling immune cell activation.

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