scholarly journals Spatially structured cell populations process multiple sensory signals in parallel in intact vascular endothelium

2018 ◽  
Vol 11 (561) ◽  
pp. eaar4411 ◽  
Author(s):  
Matthew D. Lee ◽  
Calum Wilson ◽  
Christopher D. Saunter ◽  
Charles Kennedy ◽  
John M. Girkin ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelium ◽  
Vascular Remodeling ◽  
Blood Clotting ◽  
Cell Populations ◽  
Complex Environment ◽  
Complementary Information ◽  
Chemical Inputs ◽  
Enormous Quantity

Blood flow, blood clotting, angiogenesis, vascular permeability, and vascular remodeling are each controlled by a large number of variable, noisy, and interacting chemical inputs to the vascular endothelium. The endothelium processes the entirety of the chemical composition to which the cardiovascular system is exposed, carrying out sophisticated computations that determine physiological output. Processing this enormous quantity of information is a major challenge facing the endothelium. We analyzed the responses of hundreds of endothelial cells to carbachol (CCh) and adenosine triphosphate (ATP) and found that the endothelium segregates the responses to these two distinct components of the chemical environment into separate streams of complementary information that are processed in parallel. Sensitivities to CCh and ATP mapped to different clusters of cells, and each agonist generated distinct signal patterns. The distinct signals were features of agonist activation rather than properties of the cells themselves. When there was more than one stimulus present, the cells communicated and combined inputs to generate new distinct signals that were nonlinear combinations of the inputs. Our results demonstrate that the endothelium is a structured, collaborative sensory network that simplifies the complex environment using separate cell clusters that are sensitive to distinct aspects of the overall biochemical environment and interactively compute signals from diverse but interrelated chemical inputs. These features enable the endothelium to selectively process separate signals and perform multiple computations in an environment that is noisy and variable.

scholarly journals Blood flow boosts BMP signaling to keep vessels in shape

2016 ◽  
Vol 214 (7) ◽  
pp. 793-795 ◽  
Author(s):  
Claudio A. Franco ◽  
Holger Gerhardt
Keyword(s):  
Cell Proliferation ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Bmp Signaling ◽  
Mural Cells ◽  
Bone Morphogenic Proteins ◽  
Cell Biol ◽  
Suppress Cell Proliferation

Bone morphogenic proteins (BMPs) and blood flow regulate vascular remodeling and homeostasis. In this issue, Baeyens et al. (2016. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201603106) show that blood flow sensitizes endothelial cells to BMP9 signaling by triggering Alk1/ENG complexing to suppress cell proliferation and to recruit mural cells, thereby establishing endothelial quiescence.

scholarly journals Adipocyte-Endothelium Crosstalk in Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Rugivan Sabaratnam ◽  
Per Svenningsen
Keyword(s):  
Metabolic Disease ◽  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Endothelium ◽  
Energy Homeostasis ◽  
Cell Communication ◽  
Normal Organ ◽  
Arterial Endothelial Cells

Obesity is characterized by pathological adipose tissue (AT) expansion. While healthy AT expansion enhances systemic insulin sensitivity, unhealthy AT expansion through increased adipocyte size is associated with insulin resistance, fibrosis, hypoxia, and reduced adipose-derived adiponectin secretion. The mechanisms causing the unhealthy AT expansion are not fully elucidated; yet, dysregulated crosstalk between cells within the AT is an important contributor. Evidence from animal and human studies suggests a crucial role of the crosstalk between vascular endothelium (the innermost cell type in blood vessels) and adipocytes for metabolic homeostasis. Arterial endothelial cells are directly involved in maintaining normal organ functions through local blood flow regulation. The endothelial-dependent regulation of blood flow in AT is hampered in obesity, which negatively affects the adipocyte. Moreover, endothelial cells secrete extracellular vesicles (EVs) that target adipocytes in vivo. The endothelial EVs secretion is hampered in obesity and may be affected by the adipocyte-derived adipokine adiponectin. Adiponectin targets the vascular endothelium, eliciting organ-protective functions through binding to T-cadherin. The reduced obesity-induced adiponectin binding of T-cadherin reduces endothelial EV secretion. This affects endothelial health and cell-cell communication between AT cells and distant organs, influencing systemic energy homeostasis. This review focuses on the current understanding of endothelial and adipocyte crosstalk. We will discuss how obesity changes the AT environment and how these changes contribute to obesity-associated metabolic disease in humans. Particularly, we will describe and discuss the EV-dependent communication and regulation between adipocytes, adiponectin, and the endothelial cells regulating systemic energy homeostasis in health and metabolic disease in humans.

scholarly journals Dynamic responses of endothelial cells to changes in blood flow during vascular remodeling of the mouse yolk sac

Development ◽  
2013 ◽  
Vol 140 (19) ◽  
pp. 4041-4050 ◽  
Author(s):  
Ryan S. Udan ◽  
Tegy J. Vadakkan ◽  
Mary E. Dickinson
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Yolk Sac ◽  
Dynamic Responses

PERSPECTIVES OF APPLICATION OF ANTIBODIES AGAINST ENDOGLIN (CD105) FOR VISUALIZATION AND ANTI-ANGIOGENE THERAPY OF TUMORS

2018 ◽  
Vol 64 (4) ◽  
pp. 504-507
Author(s):  
Vladimir Klimovich ◽  
Natalya Vartanyan ◽  
Anastasiya Stolbovaya ◽  
Lidiya Terekhina ◽  
Olga Shashkova ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Monoclonal Antibodies ◽  
Human Plasma ◽  
Vascular Endothelium ◽  
Immune Complexes ◽  
Targeted Delivery ◽  
Biological Fluids ◽  
Therapeutic Drugs ◽  
Cultured Endothelial Cells ◽  
Hybridoma Technology

During last years monoclonal antibodies (MAB) directed against vascular endothelium markers demonstrated their efficiency for visualization and targeted delivery of therapeutic drugs to tumors. Endoglin (CD105) which serves as a key element that determines endothelial cells quiescence or activation is one of such markers. Endoglin is highly expressed on the vascular endothelium of growing tumors. A first panel of MAB against endoglin in our country was produced at the hybridoma technology laboratory of RRC RST named after A.M. Granov. On the basis of these MAB ELISA was created allowing detection of endoglin in human plasma and other biological fluids. Several MAB had been shown to bind endoglin on the membrane of the cultured endothelial cells and to persist there for several hours. During the first 30 min after binding some of the immune complexes “endoglin-MAB” were internalized into the cytoplasm and were found included in the endosomes. In future these MAB can be used to create the reagents for the addressed delivery of isotope tags both on the membrane and into the cytoplasm of endothelial cells.

Segregation of late outgrowth endothelial cells into functional endothelial CD34− and progenitor-like CD34+ cell populations

Angiogenesis ◽  
2014 ◽  
Vol 18 (1) ◽  
pp. 47-68 ◽  
Author(s):  
Cristina Ferreras ◽  
Claire L. Cole ◽  
Katharina Urban ◽  
Gordon C. Jayson ◽  
Egle Avizienyte
Keyword(s):  
Endothelial Cells ◽  
Cell Populations

scholarly journals Adrenergic control of vascular resistance varies in muscles composed of different fiber types: influence of the vascular endothelium

2011 ◽  
Vol 301 (3) ◽  
pp. R783-R790 ◽  
Author(s):  
Bradley J. Behnke ◽  
Robert B. Armstrong ◽  
Michael D. Delp
Keyword(s):  
Blood Flow ◽  
Vascular Resistance ◽  
Vascular Endothelium ◽  
Fold Increase ◽  
Male Rats ◽  
Type I ◽  
Fiber Types ◽  
Fast Twitch Muscle ◽  
Dose Responses ◽  
Fast Twitch

The influence of the sympathetic nervous system (SNS) upon vascular resistance is more profound in muscles comprised predominately of low-oxidative type IIB vs. high-oxidative type I fiber types. However, within muscles containing high-oxidative type IIA and IIX fibers, the role of the SNS on vasomotor tone is not well established. The purpose of this study was to examine the influence of sympathetic neural vasoconstrictor tone in muscles composed of different fiber types. In adult male rats, blood flow to the red and white portions of the gastrocnemius (GastRed and GastWhite, respectively) and the soleus muscle was measured pre- and postdenervation. Resistance arterioles from these muscles were removed, and dose responses to α1-phenylephrine or α2-clonidine adrenoreceptor agonists were determined with and without the vascular endothelium. Denervation resulted in a 2.7-fold increase in blood flow to the soleus and GastRed and an 8.7-fold increase in flow to the GastWhite. In isolated arterioles, α2-mediated vasoconstriction was greatest in GastWhite (∼50%) and less in GastRed (∼31%) and soleus (∼17%); differences among arterioles were abolished with the removal of the endothelium. There was greater sensitivity to α1-mediated vasoconstriction in the GastWhite and GastRed vs. the soleus, which was independent of whether the endothelium was present. These data indicate that 1) control of vascular resistance by the SNS in high-oxidative, fast-twitch muscle is intermediate to that of low-oxidative, fast-twitch and high-oxidative, slow-twitch muscles; and 2) the ability of the SNS to control blood flow to low-oxidative type IIB muscle appears to be mediated through postsynaptic α1- and α2-adrenoreceptors on the vascular smooth muscle.

scholarly journals Maternal Uterine Vascular Remodeling During Pregnancy

Physiology ◽  
2009 ◽  
Vol 24 (1) ◽  
pp. 58-71 ◽  
Author(s):  
George Osol ◽  
Maurizio Mandala
Keyword(s):  
Extracellular Matrix ◽  
Blood Flow ◽  
Vascular Remodeling ◽  
Normal Pregnancy ◽  
Uterine Blood Flow ◽  
Growth And Remodeling ◽  
Cellular Mechanisms ◽  
Cellular Processes ◽  
Uteroplacental Blood Flow ◽  
Uterine Circulation

Sufficient uteroplacental blood flow is essential for normal pregnancy outcome and is accomplished by the coordinated growth and remodeling of the entire uterine circulation, as well as the creation of a new fetal vascular organ: the placenta. The process of remodeling involves a number of cellular processes, including hyperplasia and hypertrophy, rearrangement of existing elements, and changes in extracellular matrix. In this review, we provide information on uterine blood flow increases during pregnancy, the influence of placentation type on the distribution of uterine vascular resistance, consideration of the patterns, nature, and extent of maternal uterine vascular remodeling during pregnancy, and what is known about the underlying cellular mechanisms.

Glycocalyx modulates the motility and proliferative response of vascular endothelium to fluid shear stress

2007 ◽  
Vol 293 (2) ◽  
pp. H1023-H1030 ◽  
Author(s):  
Yu Yao ◽  
Aleksandr Rabodzey ◽  
C. Forbes Dewey
Keyword(s):  
Endothelial Cells ◽  
Vascular Endothelium ◽  
Fluid Shear Stress ◽  
Vascular Endothelial Cells ◽  
Surface Profile ◽  
Cell Junctions ◽  
Vascular Endothelial ◽  
Fluid Shear ◽  
New Perspective ◽  
Cell Cell

Flow-induced mechanotransduction in vascular endothelial cells has been studied over the years with a major focus on putative connections between disturbed flow and atherosclerosis. Recent studies have brought in a new perspective that the glycocalyx, a structure decorating the luminal surface of vascular endothelium, may play an important role in the mechanotransduction. This study reports that modifying the amount of the glycocalyx affects both short-term and long-term shear responses significantly. It is well established that after 24 h of laminar flow, endothelial cells align in the direction of flow and their proliferation is suppressed. We report here that by removing the glycocalyx by using the specific enzyme heparinase III, endothelial cells no longer align under flow after 24 h and they proliferate as if there were no flow present. In addition, confluent endothelial cells respond rapidly to flow by decreasing their migration speed by 40% and increasing the amount of vascular endothelial cadherin in the cell-cell junctions. These responses are not observed in the cells treated with heparinase III. Heparan sulfate proteoglycans (a major component of the glycocalyx) redistribute after 24 h of flow application from a uniform surface profile to a distinct peripheral pattern with most molecules detected above cell-cell junctions. We conclude that the presence of the glycocalyx is necessary for the endothelial cells to respond to fluid shear, and the glycocalyx itself is modulated by the flow. The redistribution of the glycocalyx also appears to serve as a cell-adaptive mechanism by reducing the shear gradients that the cell surface experiences.

Adenosine inhibits cytokine release and expression of adhesion molecules by activated human endothelial cells

1996 ◽  
Vol 270 (2) ◽  
pp. C522-C529 ◽  
Author(s):  
M. G. Bouma ◽  
F. A. van den Wildenberg ◽  
W. A. Buurman
Keyword(s):  
Endothelial Cells ◽  
Adhesion Molecules ◽  
Adhesion Molecule ◽  
Vascular Endothelium ◽  
Cell Activation ◽  
Umbilical Vein ◽  
Intercellular Adhesion Molecule ◽  
Cytokine Release ◽  
Adenosine Deaminase Activity ◽  
Anti Inflammatory

Ischemia induces excessive ATP catabolism with subsequent local release of its metabolite adenosine, an autacoid with anti-inflammatory properties. Because activation of the vascular endothelium is critical to the inflammatory host response during ischemia and reperfusion, the effects of adenosine on two major determinants of endothelial cell activation (i.e., the release of proinflammatory cytokines and the expression of adhesion molecules) were studied. Adenosine dose dependently inhibited the release of interleukin (IL)-6 and IL-8 by stimulated human umbilical vein endothelial cells (HUVEC). Expression of E-selectin and vascular cell adhesion molecule 1 (VCAM-1), but not intercellular adhesion molecule 1 (ICAM-1), by activated HUVEC was also reduced by adenosine. Inhibition of endogenous adenosine deaminase activity by erythro-9-(2-hydroxy-3-nonyl)adenine or 2'-deoxycoformycin strongly enhanced the inhibitory effects of exogenous adenosine on cytokine release and expression of E-selectin and VCAM-1. However, a clear role for specific adenosine receptors in the described inhibitory events could not be established. Together, these data imply that the vascular endothelium constitutes an important target for the anti-inflammatory actions of adenosine.

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