Exosomes and cardiovascular cell–cell communication

2018 ◽  
Vol 62 (2) ◽  
pp. 193-204 ◽  
Author(s):  
Adam J. Poe ◽  
Anne A. Knowlton
Keyword(s):  
Biological Fluids ◽  
Cell Communication ◽  
Cell Types ◽  
Cardiac Cells ◽  
The Body ◽  
Biologically Active ◽  
Surrounding Tissue ◽  
Intercellular Signaling ◽  
Cardiac Damage ◽  
Almost All

Exosomes have become an important player in intercellular signaling. These lipid microvesicles can stably transfer miRNA, protein, and other molecules between cells and circulate throughout the body. Exosomes are released by almost all cell types and are present in most if not all biological fluids. The biologically active cargo carried by exosomes can alter the phenotype of recipient cells. Exosomes increasingly are recognized as having an important role in the progression and treatment of cardiac disease states. Injured cardiac cells can release exosomes with important pathological effects on surrounding tissue, in addition to effecting other organs. But of equal interest is the possible benefit(s) conferred by exosomes released from stem cells for use in treatment and possible repair of cardiac damage.

scholarly journals Unfathomed Nanomessages to the Heart: Translational Implications of Stem Cell-Derived, Progenitor Cell Exosomes in Cardiac Repair and Regeneration

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1811
Author(s):  
Charan Thej ◽  
Raj Kishore
Keyword(s):  
Cardiovascular Diseases ◽  
Progenitor Cells ◽  
Cardiac Fibroblasts ◽  
Cell Communication ◽  
Cardiac Regeneration ◽  
Cell Types ◽  
Cardiac Cells ◽  
The Body ◽  
Target Cells

Exosomes formed from the endosomal membranes at the lipid microdomains of multivesicular bodies (MVBs) have become crucial structures responsible for cell communication. This paracrine communication system between a myriad of cell types is essential for maintaining homeostasis and influencing various biological functions in immune, vasculogenic, and regenerative cell types in multiple organs in the body, including, but not limited to, cardiac cells and tissues. Characteristically, exosomes are identifiable by common proteins that participate in their biogenesis; however, many different proteins, mRNA, miRNAs, and lipids, have been identified that mediate intercellular communication and elicit multiple functions in other target cells. Although our understanding of exosomes is still limited, the last decade has seen a steep surge in translational studies involving the treatment of cardiovascular diseases with cell-free exosome fractions from cardiomyocytes (CMs), cardiosphere-derived cells (CDCs), endothelial cells (ECs), mesenchymal stromal cells (MSCs), or their combinations. However, most primary cells are difficult to culture in vitro and to generate sufficient exosomes to treat cardiac ischemia or promote cardiac regeneration effectively. Pluripotent stem cells (PSCs) offer the possibility of an unlimited supply of either committed or terminally differentiated cells and their exosomes for treating cardiovascular diseases (CVDs). This review discusses the promising prospects of treating CVDs using exosomes from cardiac progenitor cells (CPCs), endothelial progenitor cells (EPCs), MSCs, and cardiac fibroblasts derived from PSCs.

scholarly journals Glucocorticoid Receptor β (GRβ): Beyond Its Dominant-Negative Function

2021 ◽  
Vol 22 (7) ◽  
pp. 3649
Author(s):  
Patricia Ramos-Ramírez ◽  
Omar Tliba
Keyword(s):  
Current Knowledge ◽  
Inflammatory Diseases ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Dominant Negative ◽  
Negative Effects ◽  
Independent Manner ◽  
Distinct Cell ◽  
Induced Apoptosis

Glucocorticoids (GCs) act via the GC receptor (GR), a receptor ubiquitously expressed in the body where it drives a broad spectrum of responses within distinct cell types and tissues, which vary in strength and specificity. The variability of GR-mediated cell responses is further extended by the existence of GR isoforms, such as GRα and GRβ, generated through alternative splicing mechanisms. While GRα is the classic receptor responsible for GC actions, GRβ has been implicated in the impairment of GRα-mediated activities. Interestingly, in contrast to the popular belief that GRβ actions are restricted to its dominant-negative effects on GRα-mediated responses, GRβ has been shown to have intrinsic activities and “directly” regulates a plethora of genes related to inflammatory process, cell communication, migration, and malignancy, each in a GRα-independent manner. Furthermore, GRβ has been associated with increased cell migration, growth, and reduced sensitivity to GC-induced apoptosis. We will summarize the current knowledge of GRβ-mediated responses, with a focus on the GRα-independent/intrinsic effects of GRβ and the associated non-canonical signaling pathways. Where appropriate, potential links to airway inflammatory diseases will be highlighted.

Abstract 533: Lymph is a Vehicle for Extracellular Vesicles in Mice

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Andreea Milasan ◽  
Nicolas Tessandier ◽  
Sisareuth Tan ◽  
Alain Brisson ◽  
Eric Boilard ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Biological Fluids ◽  
Lymphatic Vessels ◽  
The Body ◽  
Artery Wall ◽  
Waste Products ◽  
Peripheral Tissues ◽  
Cellular Debris ◽  
Long Time ◽  
Almost All

Introduction: Although for a long time considered as simple cellular debris, extracellular vesicles (EVs) are now known to be involved in many pathophysiological processes such as thrombosis, autoimmune diseases and inflammation. Due to their diversity and presence in different tissues, EVs are considered important biomarkers and thus, their precise detection in various biological fluids is important to better understand all their different functional activities. The lymphatic system works in close collaboration with the cardiovascular system to preserve fluid balance throughout the body. Lymphatic vessels are present in almost all vascularized tissues, including the brain and the artery wall, and their role in these organ-related pathologies are under intense investigations. Hypothesis: Since lymphatic vessels are often perceived as "sewers", due to their role in removing interstitial fluid and waste products from peripheral tissues such as the artery wall, we herein want to qualitatively and quantitatively assess the presence of EVs in circulating lymph. Methods and Results: Using several approaches such as a Zetasizer Nano S, electron microscopy and flow cytometry analysis, we have detected and characterized EVs in lymph of healthy animals, and found that these EVs are inclusively derived from red blood cells, platelets and lymphatic endothelial cells. Analysis of lymph from atherosclerotic mice (Ldlr -/- ) confirmed the idea that EVs number and origin varies according to the pathological setting. Conclusion: Herein, we show for the first time that EVs are present in lymph and that their level and origin vary in atherosclerosis. Our work will be setting the stage to a better understanding of the mechanism underlying EV accumulation in peripheral tissues during inflammation, and to better control related diseases.

scholarly journals Adiponectin: a pleiotropic hormone with multifaceted roles

2021 ◽  
Vol 67 (6) ◽  
pp. 98-112
Author(s):  
S. S. Shklyaev ◽  
G. A. Melnichenko ◽  
N. N. Volevodz ◽  
N. A. Falaleeva ◽  
S. A. Ivanov ◽  
...  
Keyword(s):  
Cell Types ◽  
The Body ◽  
Biologically Active ◽  
Protective Effects ◽  
Immune Functions ◽  
Ample Evidence ◽  
Endocrine Organs ◽  
Different Types ◽  
Different Cell Types ◽  
Pleiotropic Actions

Adipose tissue mostly composed of different types of fat is one of the largest endocrine organs in the body playing multiple intricate roles including but not limited to energy storage, metabolic homeostasis, generation of heat, participation in immune functions and secretion of a number of biologically active factors known as adipokines. The most abundant of them is adiponectin. This adipocite-derived hormone exerts pleiotropic actions and exhibits insulin-sensitizing, antidiabetic, anti-obesogenic, anti-inflammatory, antiatherogenic, cardio- and neuroprotective properties. Contrariwise to its protective effects against various pathological events in different cell types, adiponectin may have links to several systemic diseases and malignances. Reduction in adiponectin levels has an implication in COVID-19-associated respiratory failure, which is attributed mainly to a phenomenon called ‘adiponectin paradox’. Ample evidence about multiple functions of adiponectin in the body was obtained from animal, mostly rodent studies. Our succinct review is entirely about multifaceted roles of adiponectin and mechanisms of its action in different physiological and pathological states.

scholarly journals Potential Diagnostic and Prognostic Biomarkers of Epigenetic Drift within the Cardiovascular Compartment

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Robert G. Wallace ◽  
Laura C. Twomey ◽  
Marc-Antoine Custaud ◽  
Niall Moyna ◽  
Philip M. Cummins ◽  
...  
Keyword(s):  
Biological Fluids ◽  
Cell Types ◽  
Lifestyle Changes ◽  
The Body ◽  
Direct Function ◽  
Disease States ◽  
Markers Of Inflammation ◽  
Wide Range ◽  
Alternative Means ◽  
New Biomarkers

Biomarkers encompass a wide range of different measurable indicators, representing a tangible link to physiological changes occurring within the body. Accessibility, sensitivity, and specificity are significant factors in biomarker suitability. New biomarkers continue to be discovered, and questions over appropriate selection and assessment of their usefulness remain. If traditional markers of inflammation are not sufficiently robust in their specificity, then perhaps alternative means of detection may provide more information. Epigenetic drift (epigenetic modifications as they occur as a direct function with age), and its ancillary elements, including platelets, secreted microvesicles (MVs), and microRNA (miRNA), may hold enormous predictive potential. The majority of epigenetic drift observed in blood is independent of variations in blood cell composition, addressing concerns affecting traditional blood-based biomarker efficacy. MVs are found in plasma and other biological fluids in healthy individuals. Altered MV/miRNA profiles may also be found in individuals with various diseases. Platelets are also highly reflective of physiological and lifestyle changes, making them extremely sensitive biomarkers of human health. Platelets release increased levels of MVs in response to various stimuli and under a plethora of disease states, which demonstrate a functional effect on other cell types.

scholarly journals Notch Signaling in Development, Tissue Homeostasis, and Disease

2017 ◽  
Vol 97 (4) ◽  
pp. 1235-1294 ◽  
Author(s):  
Chris Siebel ◽  
Urban Lendahl
Keyword(s):  
Notch Signaling ◽  
Cell Communication ◽  
Cell Types ◽  
The Body ◽  
Tissue Homeostasis ◽  
Cell Fates ◽  
Signaling Mechanism ◽  
Transmembrane Receptors ◽  
Notch Gene ◽  
Broad Variety

Notch signaling is an evolutionarily highly conserved signaling mechanism, but in contrast to signaling pathways such as Wnt, Sonic Hedgehog, and BMP/TGF-β, Notch signaling occurs via cell-cell communication, where transmembrane ligands on one cell activate transmembrane receptors on a juxtaposed cell. Originally discovered through mutations in Drosophila more than 100 yr ago, and with the first Notch gene cloned more than 30 yr ago, we are still gaining new insights into the broad effects of Notch signaling in organisms across the metazoan spectrum and its requirement for normal development of most organs in the body. In this review, we provide an overview of the Notch signaling mechanism at the molecular level and discuss how the pathway, which is architecturally quite simple, is able to engage in the control of cell fates in a broad variety of cell types. We discuss the current understanding of how Notch signaling can become derailed, either by direct mutations or by aberrant regulation, and the expanding spectrum of diseases and cancers that is a consequence of Notch dysregulation. Finally, we explore the emerging field of Notch in the control of tissue homeostasis, with examples from skin, liver, lung, intestine, and the vasculature.

scholarly journals Structure-Based Discovery of Novel Chemical Classes of Autotaxin Inhibitors

2020 ◽  
Vol 21 (19) ◽  
pp. 7002
Author(s):  
Christiana Magkrioti ◽  
Eleanna Kaffe ◽  
Elli-Anna Stylianaki ◽  
Camelia Sidahmet ◽  
Georgia Melagraki ◽  
...  
Keyword(s):  
In Silico ◽  
Rational Design ◽  
Inflammatory Diseases ◽  
Molecular Model ◽  
Biological Fluids ◽  
Cell Types ◽  
Phase Iii ◽  
Priority List ◽  
Model Docking ◽  
Almost All

Autotaxin (ATX) is a secreted glycoprotein, widely present in biological fluids, largely responsible for extracellular lysophosphatidic acid (LPA) production. LPA is a bioactive growth-factor-like lysophospholipid that exerts pleiotropic effects in almost all cell types, exerted through at least six G-protein-coupled receptors (LPAR1-6). Increased ATX expression has been detected in different chronic inflammatory diseases, while genetic or pharmacological studies have established ATX as a promising therapeutic target, exemplified by the ongoing phase III clinical trial for idiopathic pulmonary fibrosis. In this report, we employed an in silico drug discovery workflow, aiming at the identification of structurally novel series of ATX inhibitors that would be amenable to further optimization. Towards this end, a virtual screening protocol was applied involving the search into molecular databases for new small molecules potentially binding to ATX. The crystal structure of ATX in complex with a known inhibitor (HA-155) was used as a molecular model docking reference, yielding a priority list of 30 small molecule ATX inhibitors, validated by a well-established enzymatic assay of ATX activity. The two most potent, novel and structurally different compounds were further structurally optimized by deploying further in silico tools, resulting to the overall identification of six new ATX inhibitors that belong to distinct chemical classes than existing inhibitors, expanding the arsenal of chemical scaffolds and allowing further rational design.

scholarly journals Role of exosomes and exosomal microRNAs in cancer

2020 ◽  
pp. FSO465 ◽  
Author(s):  
Nihat Dilsiz
Keyword(s):  
Critical Role ◽  
Cell Communication ◽  
Average Diameter ◽  
Cell Types ◽  
Specific Protein ◽  
Communication Process ◽  
Protein Biomarkers ◽  
Double Stranded Dna ◽  
Almost All

A growing body of evidence indicates that exosomes play a critical role in the cell–cell communication process. Exosomes are biological nanoparticles with an average diameter of 30–100 nm in size and are produced by almost all cell types in the human body; however, cancer cells contain higher concentrations of exosomes than healthy cells. They are released into all body fluids and contain double-stranded DNA (originated from nucleus and mitochondria), a variety of RNA species, and specific protein biomarkers that can be utilized as cancer biomarkers and therapeutic targets, and lipids. Therefore, the specific exosomes secreted by tumor cells could be used to predict the existence of the presence of a tumor in cancer patients. This review summarizes the role of exosomes in cancer development and their potential utility in the clinic.

scholarly journals Microvesicles in bronchoalveolar lavage as a potential biomarker of COPD.

2020 ◽  
Author(s):  
Erica Bazzan ◽  
Claudia Maria Radu ◽  
Mariaenrica Tinè ◽  
Tommaso Neri ◽  
Davide Biondini ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Lung Function ◽  
Bronchoalveolar Lavage ◽  
Inflammatory Diseases ◽  
Biological Fluids ◽  
Cell Communication ◽  
Communication Tools ◽  
Inflammatory Signals ◽  
Potential Biomarker ◽  
Almost All

Background. Microvesicles (MVs) released from almost all cells are recognized as cell communication tools. MVs have been investigated in several inflammatory diseases but poorly in biological fluids like bronchoalveolar lavage (BAL) of smokers. Aims. The purpose of this study was to investigate the presence and source of MVs in BAL of smokers with and without COPD compared to non-smoking controls. Methods and Results. Using flow-cytometry in BAL we detected endothelial and Alveolar Macrophage (AM)-derived MVs, and found a higher number of AM-MVs in the BAL of smokers with COPD than in smokers without COPD and non-smokers, which correlated with the pack-years (r=0.46; p=0.05) and with the degree of airway obstruction measured by the FEV1 % predicted (r= -0.56; p=0.01). Conclusion. Endothelial and Alveolar Macrophages-derived MVs are present and measurable in human BAL fluid. In response to smoking and to the development of COPD, inflammatory signals in AM-derived MVs can be quantified, and their numbers are related to the pack-years and the decrease in lung function. These results open the opportunity for future investigation of these microvesicles as biomarkers and possible mechanistic guides in COPD.

scholarly journals Exosomes and Micro-RNAs in Aging Process

Biomedicines ◽  
2021 ◽  
Vol 9 (8) ◽  
pp. 968
Author(s):  
Yousra Hamdan ◽  
Loubna Mazini ◽  
Gabriel Malka
Keyword(s):  
Messenger Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Biological Fluids ◽  
Cell Types ◽  
Exosome Biogenesis ◽  
Age Related ◽  
Micro Rnas ◽  
Underlying Mechanisms ◽  
Almost All

Exosomes are the main actors of intercellular communications and have gained great interest in the new cell-free regenerative medicine. These nanoparticles are secreted by almost all cell types and contain lipids, cytokines, growth factors, messenger RNA, and different non-coding RNA, especially micro-RNAs (mi-RNAs). Exosomes’ cargo is released in the neighboring microenvironment but is also expected to act on distant tissues or organs. Different biological processes such as cell development, growth and repair, senescence, migration, immunomodulation, and aging, among others, are mediated by exosomes and principally exosome-derived mi-RNAs. Moreover, their therapeutic potential has been proved and reinforced by their use as biomarkers for disease diagnostics and progression. Evidence has increasingly shown that exosome-derived mi-RNAs are key regulators of age-related diseases, and their involvement in longevity is becoming a promising issue. For instance, mi-RNAs such as mi-RNA-21, mi-RNA-29, and mi-RNA-34 modulate tissue functionality and regeneration by targeting different tissues and involving different pathways but might also interfere with long life expectancy. Human mi-RNAs profiling is effectively related to the biological fluids that are reported differently between young and old individuals. However, their underlying mechanisms modulating cell senescence and aging are still not fully understood, and little was reported on the involvement of mi-RNAs in cell or tissue longevity. In this review, we summarize exosome biogenesis and mi-RNA synthesis and loading mechanism into exosomes’ cargo. Additionally, we highlight the molecular mechanisms of exosomes and exosome-derived mi-RNA regulation in the different aging processes.

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