scholarly journals Vascular Endothelial Cells: Heterogeneity and Targeting Approaches

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2712
Author(s):  
Jan K. Hennigs ◽  
Christiane Matuszcak ◽  
Martin Trepel ◽  
Jakob Körbelin
Keyword(s):  
Endothelial Cells ◽  
Immune Cell ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Treatment Options ◽  
Vascular Diseases ◽  
The Body ◽  
Liver Sinusoids ◽  
Physiological Processes ◽  
Organ Systems

Forming the inner layer of the vascular system, endothelial cells (ECs) facilitate a multitude of crucial physiological processes throughout the body. Vascular ECs enable the vessel wall passage of nutrients and diffusion of oxygen from the blood into adjacent cellular structures. ECs regulate vascular tone and blood coagulation as well as adhesion and transmigration of circulating cells. The multitude of EC functions is reflected by tremendous cellular diversity. Vascular ECs can form extremely tight barriers, thereby restricting the passage of xenobiotics or immune cell invasion, whereas, in other organ systems, the endothelial layer is fenestrated (e.g., glomeruli in the kidney), or discontinuous (e.g., liver sinusoids) and less dense to allow for rapid molecular exchange. ECs not only differ between organs or vascular systems, they also change along the vascular tree and specialized subpopulations of ECs can be found within the capillaries of a single organ. Molecular tools that enable selective vascular targeting are helpful to experimentally dissect the role of distinct EC populations, to improve molecular imaging and pave the way for novel treatment options for vascular diseases. This review provides an overview of endothelial diversity and highlights the most successful methods for selective targeting of distinct EC subpopulations.

scholarly journals Interleukin-17A Triggers the Release of Platelet-Derived Factors Driving Vascular Endothelial Cells toward a Pro-Angiogenic State

Cells ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1855
Author(s):  
Aikaterini Gatsiou ◽  
Kateryna Sopova ◽  
Alexandros Tselepis ◽  
Konstantinos Stellos
Keyword(s):  
Endothelial Cells ◽  
Immune Cell ◽  
Vascular Endothelial Cells ◽  
Interleukin 2 ◽  
Cell Subset ◽  
Aortic Ring ◽  
Inflammatory Factor ◽  
Vascular Endothelial ◽  
Monocyte Chemoattractant Protein 1 ◽  
Vascular Regeneration

Platelets comprise a highly interactive immune cell subset of the circulatory system traditionally known for their unique haemostatic properties. Although platelets are considered as a vault of growth factors, cytokines and chemokines with pivotal role in vascular regeneration and angiogenesis, the exact mechanisms by which they influence vascular endothelial cells (ECs) function remain underappreciated. In the present study, we examined the role of human IL-17A/IL-17RA axis in platelet-mediated pro-angiogenic responses. We reveal that IL-17A receptor (IL-17RA) mRNA is present in platelets transcriptome and a profound increase is documented on the surface of activated platelets. By quantifying the protein levels of several factors, involved in angiogenesis, we identified that IL-17A/IL17RA axis selectively induces the release of vascular endothelial growth factor, interleukin -2 and -4, as well as monocyte chemoattractant protein -1 from treated platelets. However, IL-17A exerted no effect on the release of IL-10, an anti-inflammatory factor with potentially anti-angiogenic properties, from platelets. Treatment of human endothelial cell two-dimensional tubule networks or three-dimensional spheroid and mouse aortic ring structures with IL-17A-induced platelet releasate evoked pro-angiogenic responses of ECs. Our findings suggest that IL-17A may critically affect platelet release of pro-angiogenic factors driving ECs towards a pro-angiogenic state.

scholarly journals Analyses of the pericyte transcriptome in ischemic skeletal muscles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yuan-chi Teng ◽  
Alfredo Leonardo Porfírio-Sousa ◽  
Giulia Magri Ribeiro ◽  
Marcela Corso Arend ◽  
Lindolfo da Silva Meirelles ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelial Cells ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Limb Ischemia ◽  
Inflammatory Cells ◽  
Cell Types ◽  
Arterial Disease ◽  
The Body ◽  
Time Points

Abstract Background Peripheral arterial disease (PAD) affects millions of people and compromises quality of life. Critical limb ischemia (CLI), which is the most advanced stage of PAD, can cause nonhealing ulcers and strong chronic pain, and it shortens the patients’ life expectancy. Cell-based angiogenic therapies are becoming a real therapeutic approach to treat CLI. Pericytes are cells that surround vascular endothelial cells to reinforce vessel integrity and regulate local blood pressure and metabolism. In the past decade, researchers also found that pericytes may function as stem or progenitor cells in the body, showing the potential to differentiate into several cell types. We investigated the gene expression profiles of pericytes during the early stages of limb ischemia, as well as the alterations in pericyte subpopulations to better understand the behavior of pericytes under ischemic conditions. Methods In this study, we used a hindlimb ischemia model to mimic CLI in C57/BL6 mice and explore the role of pericytes in regeneration. To this end, muscle pericytes were isolated at different time points after the induction of ischemia. The phenotypes and transcriptomic profiles of the pericytes isolated at these discrete time points were assessed using flow cytometry and RNA sequencing. Results Ischemia triggered proliferation and migration and upregulated the expression of myogenesis-related transcripts in pericytes. Furthermore, the transcriptomic analysis also revealed that pericytes induce or upregulate the expression of a number of cytokines with effects on endothelial cells, leukocyte chemoattraction, or the activation of inflammatory cells. Conclusions Our findings provide a database that will improve our understanding of skeletal muscle pericyte biology under ischemic conditions, which may be useful for the development of novel pericyte-based cell and gene therapies.

Biomechanical interactions of Schistosoma mansoni eggs with vascular endothelial cells facilitate egg extravasation

2021 ◽  
Author(s):  
Yi-Ting Yeh ◽  
Danielle E. Skinner ◽  
Ernesto Criado-Hidalgo ◽  
Natalie Shee Chen ◽  
Antoni Garcia-De Herreros ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Schistosoma Mansoni ◽  
Disease Transmission ◽  
Vascular Endothelial Cells ◽  
Flexible Substrate ◽  
Blood Stream ◽  
The Body ◽  
Dependent Manner ◽  
Vascular Endothelial ◽  
Maturation State

AbstractThe eggs of the parasitic blood fluke, Schistosoma, are the main drivers of the chronic pathologies associated with schistosomiasis, a disease of poverty afflicting approximately 220 million people worldwide. Eggs laid by Schistosoma mansoni in the bloodstream of the host are encapsulated by vascular endothelial cells (VECs), the first step in the migration of the egg from the blood stream into the lumen of the gut and eventual exit from the body. The biomechanics associated with encapsulation and extravasation of the egg are poorly understood. We demonstrate that S. mansoni eggs induce VECs to form two types of membrane extensions during encapsulation; filopodia that probe eggshell surfaces and intercellular nanotubes that presumably facilitate VEC communication. Encapsulation efficiency, the number of filopodia and intercellular nanotubes, and the length of these structures depend on the egg’s vitality and, to a lesser degree, its maturation state. During encapsulation, live eggs induce VEC contractility and membranous structures formation, in a Rho/ROCK pathway-dependent manner. Using elastic hydrogels embedded with fluorescent microbeads as substrates to culture VECs, live eggs induce VECs to exert significantly greater contractile forces during encapsulation than dead eggs, which leads to 3D deformations on both the VEC monolayer and the flexible substrate underneath. These significant mechanical deformations cause the VEC monolayer tension to fluctuate with eventual rupture of VEC junctions, thus facilitating egg transit out of the blood vessel. Overall, our data on the mechanical interplay between host VECs and the schistosome egg improve our understanding of how this parasite manipulates its immediate environment to maintain disease transmission.

Abstract 267: Hemoglobin, Endothelial Cells, and TLRs. Common Connection?

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Christina Lisk ◽  
David Irwin
Keyword(s):  
Endothelial Cells ◽  
Messenger Rna ◽  
Time Course ◽  
Vascular Endothelial Cells ◽  
Vascular Diseases ◽  
Luciferase Reporter ◽  
Signaling Cascade ◽  
Pulmonary Vascular Disease ◽  
Luciferase Reporter Gene ◽  
Pulmonary Arterial

Introduction: Patients suffering from chronic hereditary hemolytic anemic syndromes, such as sickle cell disease (SCD) and thalassemia, are often at risk for systemic and pulmonary vascular disease. It has been suggested that chronic exposure to cell free hemoglobin (CFH) may contribute to some vascular diseases associated with these syndromes such as pulmonary arterial hypertension. To date, the vasculotoxic effects of CFH have mostly been attributed to its pro-oxidant and nitric oxide scavenging characteristics. However, emerging evidence suggests CFH may contribute to inflammation by directly activating a signaling cascade event by binding to a pattern recognition receptor (PRR) or a toll like receptor (TLR) on vascular endothelial cells. Hypothesis: We hypothesized that CFH would increase the activity of transcription factors, NF-κb and HIF-1α, via a MyD88-dependent pathway. Methods: Human microvascular endothelial cells (HMEC) were transfected with either an NF-κB or HIF-1α luciferase reporter gene and treated with CFH (ferrous, ferric, and ferryl forms) in the presence or absence of SOD, catalase, dexamethasome, MyD88 inhibitor, or, the PHD inhibitor, DMOG. Messenger RNA for HIF-1α and HIF-2 were also measured after treatments. Results: All three states of hemoglobin increased NF-κB and HIF-1α activity in a dose response fashion, with ferryl inducing the greatest activity of both NF-κB and HIF-1α. Time course studies showed that NF-κB and HIF-1α activity tracked together. A unique synergy was noted with co-treatment of ferryl and DMOG. Co-treatment with SOD or catalase did not inhibit the CFH-induced NF-κB or HIF-1α response. Dexamthasome and MyD88 inhibition reduced the CFH-induced NF-κB and HIF-1α activity. Conclusion: Our results support the hypothesis, that CFH may activate a TLR or PRR signaling cascade subsequently activating MyD88-NF-κB and HIF-1α. Our data, that showed SOD and/or catalase did not block CFH effects, suggests that this event is not mediated by CFH pro-oxidant characteristics. CFH-induced HIF-1α was blocked by NF-κB inhibition with either, Dexamethasome or MyD88 inhibition emphasizing the importance of NF-κB in the HIF-1α pathway.

scholarly journals Neuro–Immune Cell Units: A New Paradigm in Physiology

2019 ◽  
Vol 37 (1) ◽  
pp. 19-46 ◽  
Author(s):  
Cristina Godinho-Silva ◽  
Filipa Cardoso ◽  
Henrique Veiga-Fernandes
Keyword(s):  
Adipose Tissue ◽  
Paradigm Shift ◽  
Tissue Repair ◽  
Immune Cell ◽  
The Body ◽  
New Paradigm ◽  
Environmental Signals ◽  
The Past ◽  
Physiological Processes ◽  
The Impact

The interplay between the immune and nervous systems has been acknowledged in the past, but only more recent studies have started to unravel the cellular and molecular players of such interactions. Mounting evidence indicates that environmental signals are sensed by discrete neuro–immune cell units (NICUs), which represent defined anatomical locations in which immune and neuronal cells colocalize and functionally interact to steer tissue physiology and protection. These units have now been described in multiple tissues throughout the body, including lymphoid organs, adipose tissue, and mucosal barriers. As such, NICUs are emerging as important orchestrators of multiple physiological processes, including hematopoiesis, organogenesis, inflammation, tissue repair, and thermogenesis. In this review we focus on the impact of NICUs in tissue physiology and how this fast-evolving field is driving a paradigm shift in our understanding of immunoregulation and organismal physiology.

Cardiovascular Effects of Endothelin

Physiology ◽  
1997 ◽  
Vol 12 (3) ◽  
pp. 113-117
Author(s):  
JD Grossman ◽  
JP Morgan
Keyword(s):  
Endothelial Cells ◽  
Heart Disease ◽  
Vascular Endothelial Cells ◽  
Cardiovascular Effects ◽  
Multiple Organ ◽  
Vascular Endothelial ◽  
Cellular Calcium ◽  
Organ Systems

Endothelin is a potent vasoconstricting agent released by vascular endothelial cells. Endothelin affects multiple organ systems and occurs at high levels with heart disease. Changes in cellular calcium levels and Ca2+ sensitization of myofilaments mediate the endothelin pathway. The ability to modulate endothelin levels may lead to many effective therapies.

Wall Shear Stress Measurements in an Arterial Flow Bioreactor

2011 ◽  
Author(s):  
Elizabeth Voigt ◽  
Cara Buchanan ◽  
Jaime Schmieg ◽  
M. Nichole Rylander ◽  
Pavlos Vlachos
Keyword(s):  
Endothelial Cells ◽  
Shear Stress ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Shear Stresses ◽  
Bulk Flow Rate ◽  
Wall Shear ◽  
Endothelial Cell Response ◽  
And Function

Physiological flow parameters such as pressure and stress inside the vascular system strongly influence the physiology and function of vascular endothelial cells [1]. Variations in the shear stress experienced by endothelial cells affect morphology, alignment with the flow, mechanical strength, rate of proliferation, and gene expression [2]. Although it is known that these factors are dependent on the hemodynamics of the flow, the relationship has not been accurately quantified. In vitro bioreactor flow loops have been developed to simulate vascular flow for tissue conditioning and measurement of the endothelial cell response to varying shear [3–5]; however, wall shear stresses (WSS) have been estimated from the bulk flow rate by assuming Poiseuille flow [2, 6]. Due to the pulsatility of the flow, biochemical interactions, and the typically short vessel length, this assumption is fundamentally incorrect; however, the level of inaccuracy has not been quantified.

scholarly journals Development and Application of Endothelial Cells Derived From Pluripotent Stem Cells in Microphysiological Systems Models

2021 ◽  
Vol 8 ◽  
Author(s):  
Crystal C. Kennedy ◽  
Erin E. Brown ◽  
Nadia O. Abutaleb ◽  
George A. Truskey
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Blood Vessels ◽  
Pluripotent Stem Cells ◽  
The Body ◽  
Organ Systems ◽  
Temporal Waveform ◽  
Induced Pluripotent

The vascular endothelium is present in all organs and blood vessels, facilitates the exchange of nutrients and waste throughout different organ systems in the body, and sets the tone for healthy vessel function. Mechanosensitive in nature, the endothelium responds to the magnitude and temporal waveform of shear stress in the vessels. Endothelial dysfunction can lead to atherosclerosis and other diseases. Modeling endothelial function and dysfunction in organ systems in vitro, such as the blood–brain barrier and tissue-engineered blood vessels, requires sourcing endothelial cells (ECs) for these biomedical engineering applications. It can be difficult to source primary, easily renewable ECs that possess the function or dysfunction in question. In contrast, human pluripotent stem cells (hPSCs) can be sourced from donors of interest and renewed almost indefinitely. In this review, we highlight how knowledge of vascular EC development in vivo is used to differentiate induced pluripotent stem cells (iPSC) into ECs. We then describe how iPSC-derived ECs are being used currently in in vitro models of organ function and disease and in vivo applications.

Heparinoids and cellular interactions in the vascular system

1996 ◽  
Vol 16 (01) ◽  
pp. 28-34
Author(s):  
K. T. Preissner
Keyword(s):  
Heparan Sulfate ◽  
Vascular System ◽  
Vascular Diseases ◽  
Basement Membranes ◽  
Heparan Sulfate Proteoglycans ◽  
The Body ◽  
Pharmacological Intervention ◽  
Cellular Interactions ◽  
Heparin Binding ◽  
Core Proteins

SummaryHeparin and related polysaccharides have long been used for therapautic intervention in different disease states related to thromboembolic complications. The localization and functional availability of heparin-like components in the body is mostly confined to cell surfaces and extracellular matrix/basement membranes. Their strategic position particularly in the vascular system enables heparinoids linked to various core proteins (designated as heparan sulfate proteoglycans) to interact with a variety of heparin-binding proteins such as apolipoproteins, lipases, proteases and protease inhibitors, matrix proteins as well as surface receptors on other cells and microorganisms. The variety in gene expression of respective core proteins and differences in glycosaminoglycan side chains are relevant factors for the selectivity of these interactions. Heparinoid-associated core proteins serve as co-receptors for a number of metabolic properties of vascular cells as well as for the regulation of cellular processes, particular as they relate to cell growth and differentiation in angiogenesis. Moreover, heparan sulfate proteoglycans contribute to the process of lipoprotein retention in the vessel wall and the onset of atherosclerosis. Elucidation of molecular properties, functions and their role in vascular diseases can lead to valuable information for the design of heparinoid analogues to be used for pharmacological intervention.

Indian hedgehog activates hematopoiesis and vasculogenesis and can respecify prospective neurectodermal cell fate in the mouse embryo

Development ◽  
2001 ◽  
Vol 128 (10) ◽  
pp. 1717-1730 ◽  
Author(s):  
M.A. Dyer ◽  
S.M. Farrington ◽  
D. Mohn ◽  
J.R. Munday ◽  
M.H. Baron
Keyword(s):  
Endothelial Cells ◽  
Cell Fate ◽  
Mouse Embryo ◽  
Hedgehog Signaling ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Indian Hedgehog ◽  
Vascular Endothelial ◽  
Primitive Endoderm ◽  
Genes Encoding

During gastrulation in the mouse, mesoderm is induced and patterned by secreted signaling molecules, giving rise first to primitive erythroblasts and vascular endothelial cells. We have demonstrated previously that development of these lineages requires a signal(s) secreted from the adjacent primitive endoderm. We now show that Indian hedgehog (Ihh) is a primitive endoderm-secreted signal that alone is sufficient to induce formation of hematopoietic and endothelial cells. Strikingly, as seen with primitive endoderm, Ihh can respecify prospective neural ectoderm (anterior epiblast) along hematopoietic and endothelial (posterior) lineages. Downstream targets of the hedgehog signaling pathway (the genes encoding patched, smoothened and Gli1) are upregulated in anterior epiblasts cultured in the presence of Ihh protein, as is Bmp4, which may mediate the effects of Ihh. Blocking Ihh function in primitive endoderm inhibits activation of hematopoiesis and vasculogenesis in the adjacent epiblast, suggesting that Ihh is an endogenous signal that plays a key role in the development of the earliest hemato-vascular system. To our knowledge, these are the earliest functions for a hedgehog protein in post-implantation development in the mouse embryo.

Sign in / Sign up

Export Citation Format

Share Document