scholarly journals The Endothelium and Its Role in Regulating Vascular Tone

2010 ◽  
Vol 4 (1) ◽  
pp. 302-312 ◽  
Author(s):  
Aamer Sandoo ◽  
Jet J.C.S Veldhuijzen van Zanten ◽  
George S Metsios ◽  
Douglas Carroll ◽  
George D Kitas

The endothelium forms an important part of the vasculature and is involved in promoting an atheroprotective environment via the complementary actions of endothelial cell-derived vasoactive factors. Disruption of vascular homeostasis can lead to the development of endothelial dysfunction which in turn contributes to the early and late stages of atherosclerosis. In recent years an increasing number of non-invasive vascular tests have been developed to assess vascular structure and function in different clinical populations. The present review aims to provide an insight into the anatomy of the vasculature as well as the underlying endothelial cell physiology. In addition, an in-depth overview of the current methods used to assess vascular function and structure is provided as well as their link to certain clinical populations.

2001 ◽  
Vol 281 (5) ◽  
pp. C1422-C1433 ◽  
Author(s):  
Troy Stevens ◽  
Robert Rosenberg ◽  
William Aird ◽  
Thomas Quertermous ◽  
Frances L. Johnson ◽  
...  

Endothelium critically regulates systemic and pulmonary vascular function, playing a central role in hemostasis, inflammation, vasoregulation, angiogenesis, and vascular growth. Indeed, the endothelium integrates signals originating in the circulation with those in the vessel wall to coordinate vascular function. This highly metabolic role differs significantly from the historic view of endothelium, in which it was considered to be merely an inert barrier. New lines of evidence may further change our understanding of endothelium, in regard to both its origin and function. Embryological studies suggest that the endothelium arises from different sites, including angiogenesis of endothelium from macrovascular segments and vasculogenesis of endothelium from microcirculatory segments. These findings suggest an inherent phenotypic distinction between endothelial populations based on their developmental origin. Similarly, diverse environmental cues influence endothelial cell phenotype, critical to not only normal function but also the function of a diseased vessel. Consequently, an improved understanding of site-specific endothelial cell function is essential, particularly with consideration to environmental stimuli present both in the healthy vessel and in development of vasculopathic disease states. The need to examine endothelial cell phenotypes in the context of vascular function served as the basis for a recent workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI). This report is a synopsis of pertinent topics that were discussed, and future goals and research opportunities identified by the participants of the workshop are presented.


2016 ◽  
Vol 36 (12) ◽  
pp. 1740-1749 ◽  
Author(s):  
Rachel J. Roth Flach ◽  
Chang-An Guo ◽  
Laura V. Danai ◽  
Joseph C. Yawe ◽  
Sharvari Gujja ◽  
...  

The molecular mechanisms underlying lymphatic vascular development and function are not well understood. Recent studies have suggested a role for endothelial cell (EC) mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) in developmental angiogenesis and atherosclerosis. Here, we show that constitutive loss of EC Map4k4 in mice causes postnatal lethality due to chylothorax, suggesting that Map4k4 is required for normal lymphatic vascular function. Mice constitutively lacking EC Map4k4 displayed dilated lymphatic capillaries, insufficient lymphatic valves, and impaired lymphatic flow; furthermore, primary ECs derived from these animals displayed enhanced proliferation compared with controls. Yeast 2-hybrid analyses identified the Ras GTPase-activating protein Rasa1, a known regulator of lymphatic development and lymphatic endothelial cell fate, as a direct interacting partner for Map4k4. Map4k4 silencing in ECs enhanced basal Ras and extracellular signal-regulated kinase (Erk) activities, and primary ECs lacking Map4k4 displayed enhanced lymphatic EC marker expression. Taken together, these results reveal that EC Map4k4 is critical for lymphatic vascular development by regulating EC quiescence and lymphatic EC fate.


2021 ◽  
Vol 9 ◽  
Author(s):  
Edna N. Matjuda ◽  
Godwill Azeh Engwa ◽  
Constance R. Sewani-Rusike ◽  
Benedicta N. Nkeh-Chungag

The balance between dilatory and constrictive factors is important as it keeps blood vessels in a homeostatic state. However, altered physiological processes as a result of obesity, hypertension, oxidative stress, and other cardiovascular risk factors may lead to vascular damage, causing an imbalance of vasoactive factors. Over time, the sustained imbalance of these vasoactive factors may lead to vascular dysfunction, which can be assessed by non-invasive methods, such as flow-mediated dilation, pulse wave velocity, flow-mediated slowing, retinal vessel analysis, peripheral vascular reactivity, and carotid intima-media thickness assessment. Although there is increasing prevalence of cardiovascular risk factors (obesity and hypertension) in children in sub-Saharan Africa, little is known about how this may affect vascular function. This review focuses on vasoactive factors implicated in vascular (dys)function, highlighting the determinants and consequences of vascular dysfunction. It further describes the non-invasive methods used for vascular (dys)function assessments and, last, describes the impact of cardiovascular risk factors on vascular dysfunction in children of African ancestry.


Author(s):  
Peter Sterling

The synaptic connections in cat retina that link photoreceptors to ganglion cells have been analyzed quantitatively. Our approach has been to prepare serial, ultrathin sections and photograph en montage at low magnification (˜2000X) in the electron microscope. Six series, 100-300 sections long, have been prepared over the last decade. They derive from different cats but always from the same region of retina, about one degree from the center of the visual axis. The material has been analyzed by reconstructing adjacent neurons in each array and then identifying systematically the synaptic connections between arrays. Most reconstructions were done manually by tracing the outlines of processes in successive sections onto acetate sheets aligned on a cartoonist's jig. The tracings were then digitized, stacked by computer, and printed with the hidden lines removed. The results have provided rather than the usual one-dimensional account of pathways, a three-dimensional account of circuits. From this has emerged insight into the functional architecture.


2019 ◽  
Vol 14 (6) ◽  
pp. 470-479 ◽  
Author(s):  
Nazia Parveen ◽  
Amen Shamim ◽  
Seunghee Cho ◽  
Kyeong Kyu Kim

Background: Although most nucleotides in the genome form canonical double-stranded B-DNA, many repeated sequences transiently present as non-canonical conformations (non-B DNA) such as triplexes, quadruplexes, Z-DNA, cruciforms, and slipped/hairpins. Those noncanonical DNAs (ncDNAs) are not only associated with many genetic events such as replication, transcription, and recombination, but are also related to the genetic instability that results in the predisposition to disease. Due to the crucial roles of ncDNAs in cellular and genetic functions, various computational methods have been implemented to predict sequence motifs that generate ncDNA. Objective: Here, we review strategies for the identification of ncDNA motifs across the whole genome, which is necessary for further understanding and investigation of the structure and function of ncDNAs. Conclusion: There is a great demand for computational prediction of non-canonical DNAs that play key functional roles in gene expression and genome biology. In this study, we review the currently available computational methods for predicting the non-canonical DNAs in the genome. Current studies not only provide an insight into the computational methods for predicting the secondary structures of DNA but also increase our understanding of the roles of non-canonical DNA in the genome.


2021 ◽  
Vol 22 (8) ◽  
pp. 3955
Author(s):  
László Bálint ◽  
Zoltán Jakus

Our understanding of the function and development of the lymphatic system is expanding rapidly due to the identification of specific molecular markers and the availability of novel genetic approaches. In connection, it has been demonstrated that mechanical forces contribute to the endothelial cell fate commitment and play a critical role in influencing lymphatic endothelial cell shape and alignment by promoting sprouting, development, maturation of the lymphatic network, and coordinating lymphatic valve morphogenesis and the stabilization of lymphatic valves. However, the mechanosignaling and mechanotransduction pathways involved in these processes are poorly understood. Here, we provide an overview of the impact of mechanical forces on lymphatics and summarize the current understanding of the molecular mechanisms involved in the mechanosensation and mechanotransduction by lymphatic endothelial cells. We also discuss how these mechanosensitive pathways affect endothelial cell fate and regulate lymphatic development and function. A better understanding of these mechanisms may provide a deeper insight into the pathophysiology of various diseases associated with impaired lymphatic function, such as lymphedema and may eventually lead to the discovery of novel therapeutic targets for these conditions.


Author(s):  
Daniel Elieh Ali Komi ◽  
Wolfgang M. Kuebler

AbstractMast cells (MCs) are critically involved in microbial defense by releasing antimicrobial peptides (such as cathelicidin LL-37 and defensins) and phagocytosis of microbes. In past years, it has become evident that in addition MCs may eliminate invading pathogens by ejection of web-like structures of DNA strands embedded with proteins known together as extracellular traps (ETs). Upon stimulation of resting MCs with various microorganisms, their products (including superantigens and toxins), or synthetic chemicals, MCs become activated and enter into a multistage process that includes disintegration of the nuclear membrane, release of chromatin into the cytoplasm, adhesion of cytoplasmic granules on the emerging DNA web, and ejection of the complex into the extracellular space. This so-called ETosis is often associated with cell death of the producing MC, and the type of stimulus potentially determines the ratio of surviving vs. killed MCs. Comparison of different microorganisms with specific elimination characteristics such as S pyogenes (eliminated by MCs only through extracellular mechanisms), S aureus (removed by phagocytosis), fungi, and parasites has revealed important aspects of MC extracellular trap (MCET) biology. Molecular studies identified that the formation of MCET depends on NADPH oxidase-generated reactive oxygen species (ROS). In this review, we summarize the present state-of-the-art on the biological relevance of MCETosis, and its underlying molecular and cellular mechanisms. We also provide an overview over the techniques used to study the structure and function of MCETs, including electron microscopy and fluorescence microscopy using specific monoclonal antibodies (mAbs) to detect MCET-associated proteins such as tryptase and histones, and cell-impermeant DNA dyes for labeling of extracellular DNA. Comparing the type and biofunction of further MCET decorating proteins with ETs produced by other immune cells may help provide a better insight into MCET biology in the pathogenesis of autoimmune and inflammatory disorders as well as microbial defense.


Genes ◽  
2021 ◽  
Vol 12 (4) ◽  
pp. 465
Author(s):  
Colleen A. Mangold ◽  
David P. Hughes

Many organisms are able to elicit behavioral change in other organisms. Examples include different microbes (e.g., viruses and fungi), parasites (e.g., hairworms and trematodes), and parasitoid wasps. In most cases, the mechanisms underlying host behavioral change remain relatively unclear. There is a growing body of literature linking alterations in immune signaling with neuron health, communication, and function; however, there is a paucity of data detailing the effects of altered neuroimmune signaling on insect neuron function and how glial cells may contribute toward neuron dysregulation. It is important to consider the potential impacts of altered neuroimmune communication on host behavior and reflect on its potential role as an important tool in the “neuro-engineer” toolkit. In this review, we examine what is known about the relationships between the insect immune and nervous systems. We highlight organisms that are able to influence insect behavior and discuss possible mechanisms of behavioral manipulation, including potentially dysregulated neuroimmune communication. We close by identifying opportunities for integrating research in insect innate immunity, glial cell physiology, and neurobiology in the investigation of behavioral manipulation.


2019 ◽  
Vol 29 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Zahra Hoodbhoy ◽  
Nuruddin Mohammed ◽  
Nadeem Aslam ◽  
Urooj Fatima ◽  
Salima Ashiqali ◽  
...  

AbstractObjective:The objective of this study was to assess differences in myocardial systolic and diastolic function and vascular function in children 2−5 years of age born to diabetic as compared to non-diabetic mothers.Methods:This study was a retrospective cohort conducted in 2016 at The Aga Khan University Hospital, Karachi, Pakistan. It included children between 2 and 5 years of age born to mothers with and without exposure to diabetes in utero (n = 68 in each group) and who were appropriate for gestational age. Myocardial morphology and function using echocardiogram and carotid intima media thickness (cIMT) and pulse wave velocity was performed to evaluate cardiac function as well as macrovascular remodelling in these children. Multiple linear regression was used to compare the groups.Results:There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macrovascular assessment between the exposed and unexposed groups of AGA children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (median [IQR] = 1.7 [1.6–1.9] and 1.56 [1.4–1.7], respectively, p = 0.02), and a higher cIMT in children whose mothers were on medication as compared to controls (0.48 [0.44–0.52] and 0.46 [0.44–0.50], respectively, p = 0.03).Conclusion:In utero exposure to uncontrolled maternal diabetes has an effect on the cardiovascular structure and function in children aged 2−5 years. However, future work requires long-term follow-up from fetal to adult life to assess these changes over the life course.


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