Immuno-metabolic interfaces in cardiac disease and failure

2021 ◽  
Author(s):  
Edoardo Bertero ◽  
Jan Dudek ◽  
Clement Cochain ◽  
Murilo Delgobo ◽  
Gustavo Ramos ◽  
...  
Keyword(s):  
Heart Failure ◽  
New Technologies ◽  
Cell Function ◽  
Immune Cell ◽  
Wide Spectrum ◽  
Cardiac Metabolism ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
System Metabolism

Abstract The interplay between the cardiovascular system, metabolism, and inflammation plays a central role in the pathophysiology of a wide spectrum of cardiovascular diseases, including heart failure. Here, we provide an overview of the fundamental aspects of the interrelation between inflammation and metabolism, ranging from the role of metabolism in immune cell function to the processes how inflammation modulates systemic and cardiac metabolism. Furthermore, we discuss how disruption of this immuno-metabolic interface is involved in the development and progression of cardiovascular disease, with a special focus on heart failure. Finally, we present new technologies and therapeutic approaches that have recently emerged and hold promise for the future of cardiovascular medicine.

scholarly journals Neuronal guidance proteins in cardiovascular inflammation

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.

scholarly journals The Role of Extracellular Vesicles in Cutaneous Remodeling and Hair Follicle Dynamics

2019 ◽  
Vol 20 (11) ◽  
pp. 2758 ◽  
Author(s):  
Elisa Carrasco ◽  
Gonzalo Soto-Heredero ◽  
María Mittelbrunn
Keyword(s):  
Hair Follicle ◽  
Extracellular Vesicles ◽  
Cell Function ◽  
Hair Follicles ◽  
The Body ◽  
Epithelial Stem Cells ◽  
Therapeutic Approaches ◽  
Waste Products ◽  
Efficient Treatment

Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, are cell-derived membranous structures that were originally catalogued as a way of releasing cellular waste products. Since the discovery of their function in intercellular communication as carriers of proteins, lipids, and DNA and RNA molecules, numerous therapeutic approaches have focused on the use of EVs, in part because of their minimized risk compared to cell-based therapies. The skin is the organ with the largest surface in the body. Besides the importance of its body barrier function, much attention has been paid to the skin in regenerative medicine because of its cosmetic aspect, which is closely related to disorders affecting pigmentation and the presence or absence of hair follicles. The use of exosomes in therapeutic approaches for cutaneous wound healing has been reported and is briefly reviewed here. However, less attention has been paid to emerging interest in the potential capacity of EVs as modulators of hair follicle dynamics. Hair follicles are skin appendices that mainly comprise an epidermal and a mesenchymal component, with the former including a major reservoir of epithelial stem cells but also melanocytes and other cell types. Hair follicles continuously cycle, undergoing consecutive phases of resting, growing, and regression. Many biomolecules carried by EVs have been involved in the control of the hair follicle cycle and stem cell function. Thus, investigating the role of either naturally produced or therapeutically delivered EVs as signaling vehicles potentially involved in skin homeostasis and hair cycling may be an important step in the attempt to design future strategies towards the efficient treatment of several skin disorders.

scholarly journals Metabolic inflammation in heart failure with preserved ejection fraction

2020 ◽  
Author(s):  
Gabriele G Schiattarella ◽  
Daniele Rodolico ◽  
Joseph A Hill
Keyword(s):  
Heart Failure ◽  
Ejection Fraction ◽  
Cardiac Metabolism ◽  
Biological Processes ◽  
Preserved Ejection Fraction ◽  
Metabolic Inflammation ◽  
Treatment And Prevention ◽  
Metabolic Comorbidities ◽  
Inflammatory Burden

Abstract One in 10 persons in the world aged 40 years and older will develop the syndrome of HFpEF (heart failure with preserved ejection fraction), the most common form of chronic cardiovascular disease for which no effective therapies are currently available. Metabolic disturbance and inflammatory burden contribute importantly to HFpEF pathogenesis. The interplay within these two biological processes is complex; indeed, it is now becoming clear that the notion of metabolic inflammation—metainflammation—must be considered central to HFpEF pathophysiology. Inflammation and metabolism interact over the course of syndrome progression, and likely impact HFpEF treatment and prevention. Here, we discuss evidence in support of a causal, mechanistic role of metainflammation in shaping HFpEF, proposing a framework in which metabolic comorbidities profoundly impact cardiac metabolism and inflammatory pathways in the syndrome.

scholarly journals Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1255
Author(s):  
Chaorui Guo ◽  
Inga Sileikaite ◽  
Michael J. Davies ◽  
Clare L. Hawkins
Keyword(s):  
Hydrogen Peroxide ◽  
Hypochlorous Acid ◽  
Cell Function ◽  
Inflammatory Diseases ◽  
Innate Immune ◽  
Cellular Damage ◽  
Enzymatic System ◽  
Therapeutic Approaches ◽  
Macrophage Cell

Myeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wide interest in the development of therapeutic approaches to prevent HOCl-induced cellular damage including supplementation with thiocyanate (SCN−) as an alternative substrate for MPO. In this study, we used an enzymatic system composed of glucose oxidase (GO), glucose, and MPO in the absence and presence of SCN−, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H2O2) by glucose and GO results in a dose- and time-dependent decrease in metabolic activity and cell viability, and the activation of stress-related signaling pathways. Interestingly, these damaging effects were attenuated by the addition of MPO to form HOCl. Supplementation with SCN−, which favors the formation of hypothiocyanous acid, could reverse this effect. Addition of MPO also resulted in upregulation of the antioxidant gene, NAD(P)H:quinone acceptor oxidoreductase 1. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies.

scholarly journals Impact of Exercise on Immunometabolism in Multiple Sclerosis

2020 ◽  
Vol 9 (9) ◽  
pp. 3038 ◽  
Author(s):  
Remsha Afzal ◽  
Jennifer K Dowling ◽  
Claire E McCoy
Keyword(s):  
Multiple Sclerosis ◽  
Cell Function ◽  
Immune Cell ◽  
Therapeutic Benefits ◽  
Demyelinating Lesions ◽  
Inflammatory State ◽  
Autoimmune Condition ◽  
The Central Nervous System ◽  
Axonal Degradation

Multiple Sclerosis (MS) is a chronic, autoimmune condition characterized by demyelinating lesions and axonal degradation. Even though the cause of MS is heterogeneous, it is known that peripheral immune invasion in the central nervous system (CNS) drives pathology at least in the most common form of MS, relapse-remitting MS (RRMS). The more progressive forms’ mechanisms of action remain more elusive yet an innate immune dysfunction combined with neurodegeneration are likely drivers. Recently, increasing studies have focused on the influence of metabolism in regulating immune cell function. In this regard, exercise has long been known to regulate metabolism, and has emerged as a promising therapy for management of autoimmune disorders. Hence, in this review, we inspect the role of key immunometabolic pathways specifically dysregulated in MS and highlight potential therapeutic benefits of exercise in modulating those pathways to harness an anti-inflammatory state. Finally, we touch upon current challenges and future directions for the field of exercise and immunometabolism in MS.

Molecular Pathways of Ischemic Stroke and Advanced Therapeutic Strategies

2018 ◽  
Vol 4 (1-2) ◽  
Author(s):  
Preeti Singh
Keyword(s):  
Ischemic Stroke ◽  
New Technologies ◽  
Treatment Strategies ◽  
Molecular Pathways ◽  
Therapeutic Approaches ◽  
Permanent Disability ◽  
Acute Cerebral Ischemia ◽  
Tremendous Progress ◽  
New Treatment

Ischemic stroke is a leading cause of death and permanent disability. This disease may affect any age group and especially in old age and pregnancy. All the responsible mechanisms are yet not completely understood. There is limited therapeutic intervention beyond prevention, yet tremendous progress in understanding cause of stroke at molecular level has been going on. A lot of advancement has occurred in the prevention and treatment of stroke during the past decade. In this review an update work of causeways of stroke and its therapeutic approaches have been discussed. The relevance of excitotoxicity (role of glutamate receptor), inflammation, ischemic penumbra, apoptosis, to delayed mechanisms and, damage and treatment strategies have been hasted out. Although the results among clinical studies, conflict regarding several experimental data of different therapies, and it may improve neurological outcome after acute cerebral ischemia. Along this several other interventions and new technologies such as stroke detector microwave helmet are being assessed and many other advanced techniques developed by researchers. Even the development of other novel and new treatment strategies (regarding molecular pathways and risk to benefit therapeutic ratio) for stroke are still required in future for better treatment.

scholarly journals Lessons from Cancer Immunoediting in Cutaneous Melanoma

2012 ◽  
Vol 2012 ◽  
pp. 1-14 ◽  
Author(s):  
Mariana Aris ◽  
María Marcela Barrio ◽  
José Mordoh
Keyword(s):  
Cutaneous Melanoma ◽  
Tumor Stage ◽  
Experimental Models ◽  
Tumor Evolution ◽  
Special Focus ◽  
Therapeutic Approaches ◽  
Cancer Immunoediting ◽  
Future Challenges ◽  
Continuous Feedback

We will revisit the dual role of the immune system in controlling and enabling tumor progression, known ascancer immunoediting. We will go through the different phases of this phenomenon, exposing the most relevant evidences obtained from experimental models and human clinical data, with special focus on Cutaneous Melanoma, an immunogenic tumorper excellence. We will describe the different immunotherapeutic strategies employed and consider current models accounting for tumor heterogeneity. And finally, we will propose a rational discussion of the progress made and the future challenges in the therapeutics of Cutaneous Melanoma, taking into consideration that tumor evolution is the resulting from a continuous feedback between tumor cells and their environment, and that different combinatorial therapeutic approaches can be implemented according to the tumor stage.

scholarly journals Maternal Par4 and platelets contribute to defective placenta formation in mouse embryos lacking thrombomodulin

Blood ◽  
2008 ◽  
Vol 112 (3) ◽  
pp. 585-591 ◽  
Author(s):  
Rashmi Sood ◽  
Lynette Sholl ◽  
Berend Isermann ◽  
Mark Zogg ◽  
Shaun R. Coughlin ◽  
...  
Keyword(s):  
Cell Function ◽  
Immune Cell ◽  
Fetal Loss ◽  
Trophoblast Cells ◽  
Protease Activated Receptors ◽  
Genetic Ablation ◽  
Coagulation Inhibitor ◽  
Placental Failure ◽  
New Evidence

Abstract Absence of the blood coagulation inhibitor thrombomodulin (Thbd) from trophoblast cells of the mouse placenta causes a fatal arrest of placental morphogenesis. The pathogenesis of placental failure requires tissue factor, yet is not associated with increased thrombosis and persists in the absence of fibrinogen. Here, we examine the role of alternative targets of coagulation that might contribute to the placental failure and death of Thbd−/− embryos. We demonstrate that genetic deficiency of the protease-activated receptors, Par1 or Par2, in the embryo and trophoblast cells does not prevent the death of Thbd−/− embryos. Similarly, genetic ablation of the complement pathway or of maternal immune cell function does not decrease fetal loss. In contrast, Par4 deficiency of the mother, or the absence of maternal platelets, restores normal development in one-third of Thbd-null embryos. This finding generates new evidence implicating increased procoagulant activity and thrombin generation in the demise of thrombomodulin-null embryos, and suggests that platelets play a more prominent role in placental malfunction associated with the absence of thrombomodulin than fibrin formation. Our findings demonstrate that fetal prothrombotic mutations can cause localized activation of maternal platelets at the feto-maternal interface in a mother with normal hemostatic function.

scholarly journals Histone Deacetylases in the Inflamed Intestinal Epithelium—Promises of New Therapeutic Strategies

2021 ◽  
Vol 8 ◽  
Author(s):  
Lorenz Gerbeth ◽  
Rainer Glauben
Keyword(s):  
Cell Signaling ◽  
Intestinal Epithelium ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Therapeutic Approaches ◽  
Inflammatory Conditions

The intestinal epithelium is a complex, dynamic barrier that separates luminal contents from the immune compartment while mediating nutrient absorption and controlled passage of antigens to convey oral tolerance. A compromised epithelial barrier often leads to inflammation because immune cells in the lamina propria come into direct contact with luminal antigens. Defects in epithelial cell function were also shown to be involved in the etiology of inflammatory bowel diseases. These are severe, chronically relapsing inflammatory conditions of the gastrointestinal tract that also increase the risk of developing colorectal cancer. Despite major efforts of the scientific community, the precise causes and drivers of these conditions still remain largely obscured impeding the development of a permanent cure. Current therapeutic approaches mostly focus on alleviating symptoms by targeting immune cell signaling. The protein family of histone deacetylases (HDACs) has gained increasing attention over the last years, as HDAC inhibitors were shown to be potent tumor cell suppressors and also alleviate morbid inflammatory responses. Recent research continuously identifies new roles for specific HDACs suggesting that HDACs influence the cell signaling network from many different angles. This makes HDACs very interesting targets for therapeutic approaches but predicting effects after system manipulations can be difficult. In this review, we want to provide a comprehensive overview of current knowledge about the individual roles of HDACs in the intestinal epithelium to evaluate their therapeutic potential for inflammatory conditions of the gut.

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