scholarly journals Complementary roles of mechanotransduction and inflammation in vascular homeostasis

2021 ◽  
Vol 477 (2245) ◽  
pp. 20200622
Author(s):  
Marcos Latorre ◽  
Bart Spronck ◽  
Jay D. Humphrey
Keyword(s):  
Theoretical Model ◽  
Vascular Health ◽  
Induced Hypertension ◽  
Health And Disease ◽  
Vascular Geometry ◽  
Mechanical Homeostasis ◽  
Using Data ◽  
And Function ◽  
Insight Into ◽  
Structure Properties

Arteries are exposed to relentless pulsatile haemodynamic loads, but via mechanical homeostasis they tend to maintain near optimal structure, properties and function over long periods in maturity in health. Numerous insults can compromise such homeostatic tendencies, however, resulting in maladaptations or disease. Chronic inflammation can be counted among the detrimental insults experienced by arteries, yet inflammation can also play important homeostatic roles. In this paper, we present a new theoretical model of complementary mechanobiological and immunobiological control of vascular geometry and composition, and thus properties and function. We motivate and illustrate the model using data for aortic remodelling in a common mouse model of induced hypertension. Predictions match the available data well, noting a need for increased data for further parameter refinement. The overall approach and conclusions are general, however, and help to unify two previously disparate literatures, thus leading to deeper insight into the separate and overlapping roles of mechanobiology and immunobiology in vascular health and disease.

scholarly journals Role of Biological Sex in the Cardiovascular-Gut Microbiome Axis

2022 ◽  
Vol 8 ◽  
Author(s):  
Shuangyue Li ◽  
Georgios Kararigas
Keyword(s):  
Gut Microbiota ◽  
Gut Microbiome ◽  
Microbial Composition ◽  
Biological Sex ◽  
Technological Advances ◽  
Host Health ◽  
Health And Disease ◽  
And Function ◽  
Insight Into

There has been a recent, unprecedented interest in the role of gut microbiota in host health and disease. Technological advances have dramatically expanded our knowledge of the gut microbiome. Increasing evidence has indicated a strong link between gut microbiota and the development of cardiovascular diseases (CVD). In the present article, we discuss the contribution of gut microbiota in the development and progression of CVD. We further discuss how the gut microbiome may differ between the sexes and how it may be influenced by sex hormones. We put forward that regulation of microbial composition and function by sex might lead to sex-biased disease susceptibility, thereby offering a mechanistic insight into sex differences in CVD. A better understanding of this could identify novel targets, ultimately contributing to the development of innovative preventive, diagnostic and therapeutic strategies for men and women.

scholarly journals Arterial Stiffness: Different Metrics, Different Meanings

2019 ◽  
Vol 141 (9) ◽  
Author(s):  
B. Spronck ◽  
J. D. Humphrey
Keyword(s):  
Arterial Stiffness ◽  
Theoretical Approach ◽  
Clinical Studies ◽  
Basic Science ◽  
Vascular Health ◽  
Isolated Cells ◽  
Clinical Assessments ◽  
Health And Disease ◽  
Similarities And Differences ◽  
And Function

Abstract Findings from basic science and clinical studies agree that arterial stiffness is fundamental to both the mechanobiology and the biomechanics that dictate vascular health and disease. There is, therefore, an appropriately growing literature on arterial stiffness. Perusal of the literature reveals, however, that many different methods and metrics are used to quantify arterial stiffness, and reported values often differ by orders of magnitude and have different meanings. Without clear definitions and an understanding of possible inter-relations therein, it is increasingly difficult to integrate results from the literature to glean true understanding. In this paper, we briefly review methods that are used to infer values of arterial stiffness that span studies on isolated cells, excised intact vessels, and clinical assessments. We highlight similarities and differences and identify a single theoretical approach that can be used across scales and applications and thus could help to unify future results. We conclude by emphasizing the need to move toward a synthesis of many disparate reports, for only in this way will we be able to move from our current fragmented understanding to a true appreciation of how vascular cells maintain, remodel, or repair the arteries that are fundamental to cardiovascular properties and function.

scholarly journals Genetic Background Dictates Aortic Fibrosis in Hypertensive Mice

2019 ◽  
Author(s):  
Bart Spronck ◽  
Marcos Latorre ◽  
Sameet Mehta ◽  
Alexander W. Caulk ◽  
Abhay B. Ramachandra ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Wall Stress ◽  
Biomechanical Properties ◽  
Background Strain ◽  
Induced Hypertension ◽  
Before And After ◽  
Mechanical Homeostasis ◽  
And Function ◽  
Aortic Remodeling ◽  
Muscle Contractile

AbstractMany genetic mutations affect aortic structure and function in mice, but little is known about the influence of background strain. We phenotyped aortas from C57BL/6J and 129SvEv mice before and after continuous infusion of angiotensin II (AngII) for two weeks, which elevated blood pressure similarly in both strains (1.34-fold vs. 1.32-fold, systolic). Excised thoracic aortas were characterized functionally using isobaric vasoactive and cyclic passive stiffness tests whereas immunohistological studies quantified altered medial and adventitial composition as well as the infiltration of pan-inflammatory CD45+ cells. Baseline aortic geometry, composition, and biomechanical properties were similar across strains, consistent with mechanical homeostasis. Yet, aortic remodeling in response to AngII-induced hypertension differed dramatically between strains, with gross maladaptive remodeling in C57BL/6J but not in 129SvEv mice. CD45+ cell density was markedly higher in C57BL/6J than 129SvEv aortas while vasoconstrictive responses to AngII were greater in 129SvEv than C57BL/6J both before and after hypertension; importantly, smooth muscle mediated vasoconstriction reduces pressure-induced wall stress. Bulk RNA sequencing, layer-specific biomechanical modeling, and growth and remodeling simulations support the emergent hypothesis that mechanical stress-mediated immune processes promote maladaptive remodeling while smooth muscle contractile processes reduce wall stress and thereby protect against fibrosis. Differentially expressed mechano-sensitive genes thus play key roles in the distinct hypertensive aortic remodeling in C57BL/6J and 129SvEv mice and must be considered when comparing studies in different background strains, particularly mixed strains that are often used to generate mice with targeted mutations.Graphical Abstract

scholarly journals Linking structure and function in striatum using algebraic topology, digital microcircuit reconstruction and simulations of the healthy and diseased network

2021 ◽  
Author(s):  
Ilaria Carannante ◽  
Martina Scolamiero ◽  
Alexander Kozlov ◽  
Lihao Guo ◽  
Johannes Hjorth ◽  
...  
Keyword(s):  
Algebraic Topology ◽  
Network Dynamics ◽  
Structural Connectivity ◽  
Projection Neurons ◽  
Digital Reconstruction ◽  
Striatal Projection Neurons ◽  
Structural And Functional Properties ◽  
Health And Disease ◽  
Using Data ◽  
And Function

The relationship between the structure and network dynamics within the striatum is currently not well understood. We have applied algebraic topology to investigate the local structural connectivity in the striatum, and then used simulations to predict how structure shapes network dynamics. We used a full-scale digital reconstruction of the mouse striatal microcircuitry: both healthy and at different stages of Parkinson’s Disease (PD). These stages are characterized by successively modified healthy morphologies of the striatal projection neurons (SPN), including changes in dendritic spine count. We compared the distribution of topological motifs, in the form of directed cliques, between these microcircuits. The distribution of directed cliques in the healthy striatal microcircuits showed that striatal interneurons, despite only accounting for 5%, are crucial for the construction of high dimensional directed cliques. In PD networks the presence of directed cliques drastically decreased with the disease progression. We then used simulations to investigate whether these changes in structural connectivity affect functional connectivity. Signal transfer, especially correlation transfer, in the corticostriatal system was affected. We also found that the resulting changes in intrastriatal inhibition altered the correlations between the striatal projection neurons. Directed cliques already provided insight on structural and functional properties of neocortical micrucircuitry. Here we applied this topological approach to investigate striatal networks and highligthed important differences with respect to neocortex. Combining theory with simulations using data-driven in silico reconstructions will allow us to form quantitative predictions on how structure and network dynamics relate in health and disease.

The δ subunit of Epithelial sodium channel in humans - a potential player in vascular physiology

2020 ◽  
Author(s):  
Puja Paudel ◽  
Fiona J McDonald ◽  
Martin Fronius
Keyword(s):  
Vascular Function ◽  
Drug Target ◽  
Mammalian Species ◽  
Physiological Role ◽  
Vascular Health ◽  
Cardiovascular Research ◽  
Α Subunit ◽  
Vascular Physiology ◽  
Health And Disease ◽  
And Function

Vascular epithelial Na+ channels (ENaCs) made up of canonical α, β, and γ subunits have attracted more attention recently due to their physiological role in vascular health and disease. A fourth subunit δ-ENaC is expressed in various mammalian species, except mice and rats, which are common animal models for cardiovascular research. Accordingly, δ-ENaC is the least understood subunit. However, the recent discovery of δ subunit in human vascular cells indicates that this subunit may play a significant role in normal/pathological vascular physiology in humans. Channels containing the δ subunit have different biophysical and pharmacological properties compared to channels containing the α subunit, with the potential to alter the vascular function of ENaC in health and disease. Hence, it is important to investigate the expression and function of δ-ENaC in the vasculature to identify whether δ-ENaC is a potential new drug target for the treatment of cardiovascular disease. In this review, we will focus on the existing knowledge of δ-ENaC and implications for vascular physiology and pathophysiology in humans.

Structure and function of neural networks in the retina

1988 ◽  
Vol 46 ◽  
pp. 26-27
Author(s):  
Peter Sterling
Keyword(s):  
Ganglion Cells ◽  
Three Dimensional ◽  
Structure And Function ◽  
Synaptic Connections ◽  
Visual Axis ◽  
One Dimensional ◽  
Cat Retina ◽  
Ultrathin Sections ◽  
And Function ◽  
Insight Into

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.

The Laryngeal Epithelium in Reflux

2011 ◽  
Vol 21 (3) ◽  
pp. 112-117 ◽  
Author(s):  
Elizabeth Erickson-Levendoski ◽  
Mahalakshmi Sivasankar
Keyword(s):  
Laryngopharyngeal Reflux ◽  
Critical Role ◽  
Structure And Function ◽  
Laryngeal Disease ◽  
Health And Disease ◽  
And Function ◽  
The Impact

The epithelium plays a critical role in the maintenance of laryngeal health. This is evident in that laryngeal disease may result when the integrity of the epithelium is compromised by insults such as laryngopharyngeal reflux. In this article, we will review the structure and function of the laryngeal epithelium and summarize the impact of laryngopharyngeal reflux on the epithelium. Research investigating the ramifications of reflux on the epithelium has improved our understanding of laryngeal disease associated with laryngopharyngeal reflux. It further highlights the need for continued research on the laryngeal epithelium in health and disease.

“Because every recipient is also a potential patient” – TV Health Programmes in the FRG and the GDR, from the 1960s to the 1980s

Gesnerus ◽  
2019 ◽  
Vol 76 (2) ◽  
pp. 172-191
Author(s):  
Susanne Vollberg
Keyword(s):  
Public Awareness ◽  
West Germany ◽  
Continuous Coverage ◽  
Public Consciousness ◽  
Television Programme ◽  
East German ◽  
Health And Disease ◽  
Media Systems ◽  
The 1960S ◽  
And Function

In the television programme of West Germany from the 1960s to the 1980s, health magazines like Gesundheitsmagazin Praxis [Practice Health Magazine] (produced by ZDF)1 or ARD-Ratgeber: Gesundheit [ARD Health Advisor] played an important role in addressing health and disease as topics of public awareness. With their health magazine Visite [Doctor’s rounds], East German television, too relied on continuous coverage and reporting in the field. On the example of above magazines, this paper will examine the history, design and function of health communication in magazine-type formats. Before the background of the changes in media policy experienced over three decades and the different media systems in the then two Germanys, it will discuss the question of whether television was able to move health relevant topics and issues into public consciousness.

Computational Approaches to Predict the Non-canonical DNAs

2019 ◽  
Vol 14 (6) ◽  
pp. 470-479 ◽  
Author(s):  
Nazia Parveen ◽  
Amen Shamim ◽  
Seunghee Cho ◽  
Kyeong Kyu Kim
Keyword(s):  
Computational Methods ◽  
Genetic Instability ◽  
Computational Prediction ◽  
Structure And Function ◽  
Sequence Motifs ◽  
Computational Approaches ◽  
Functional Roles ◽  
And Function ◽  
Genetic Events ◽  
Insight Into

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.

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