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.

scholarly journals Maturation of the Na,K-ATPase in the Endoplasmic Reticulum in Health and Disease

2021 ◽  
Author(s):  
Vitalii Kryvenko ◽  
Olga Vagin ◽  
Laura A. Dada ◽  
Jacob I. Sznajder ◽  
István Vadász
Keyword(s):  
Endoplasmic Reticulum ◽  
Intracellular Signaling ◽  
Loss Of Function ◽  
Α Subunit ◽  
Rate Limiting Step ◽  
Atpase Subunits ◽  
A Cell ◽  
Health And Disease ◽  
And Function ◽  
Rate Limiting

Abstract The Na,K-ATPase establishes the electrochemical gradient of cells by driving an active exchange of Na+ and K+ ions while consuming ATP. The minimal functional transporter consists of a catalytic α-subunit and a β-subunit with chaperon activity. The Na,K-ATPase also functions as a cell adhesion molecule and participates in various intracellular signaling pathways. The maturation and trafficking of the Na,K-ATPase include co- and post-translational processing of the enzyme in the endoplasmic reticulum (ER) and the Golgi apparatus and subsequent delivery to the plasma membrane (PM). The ER folding of the enzyme is considered as the rate-limiting step in the membrane delivery of the protein. It has been demonstrated that only assembled Na,K-ATPase α:β-complexes may exit the organelle, whereas unassembled, misfolded or unfolded subunits are retained in the ER and are subsequently degraded. Loss of function of the Na,K-ATPase has been associated with lung, heart, kidney and neurological disorders. Recently, it has been shown that ER dysfunction, in particular, alterations in the homeostasis of the organelle, as well as impaired ER-resident chaperone activity may impede folding of Na,K-ATPase subunits, thus decreasing the abundance and function of the enzyme at the PM. Here, we summarize our current understanding on maturation and subsequent processing of the Na,K-ATPase in the ER under physiological and pathophysiological conditions. Graphic Abstract

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 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 New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Ashley Dawson ◽  
Yidan Wang ◽  
Yanming Li ◽  
Scott A. LeMaire ◽  
Ying H. Shen
Keyword(s):  
Vascular Function ◽  
Cardiovascular Health ◽  
New Technologies ◽  
Vascular Dysfunction ◽  
Vascular Wall ◽  
Vascular Health ◽  
Different Types ◽  
Endothelial Cell Heterogeneity ◽  
Health And Disease ◽  
Vessel Integrity

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.

scholarly journals Sex differences in vascular physiology and pathophysiology: estrogen and androgen signaling in health and disease

2017 ◽  
Vol 313 (3) ◽  
pp. H524-H545 ◽  
Author(s):  
Austin C. Boese ◽  
Seong C. Kim ◽  
Ke-Jie Yin ◽  
Jean-Pyo Lee ◽  
Milton H. Hamblin
Keyword(s):  
Sex Differences ◽  
Vascular Function ◽  
Cerebral Aneurysms ◽  
Cellular Tissue ◽  
Normal Function ◽  
Aortic Aneurysms ◽  
Biomedical Sciences ◽  
Vascular Physiology ◽  
Health And Disease ◽  
Artery Disease

Sex differences between women and men are often overlooked and underappreciated when studying the cardiovascular system. It has been long assumed that men and women are physiologically similar, and this notion has resulted in women being clinically evaluated and treated for cardiovascular pathophysiological complications as men. Currently, there is increased recognition of fundamental sex differences in cardiovascular function, anatomy, cell signaling, and pathophysiology. The National Institutes of Health have enacted guidelines expressly to gain knowledge about ways the sexes differ in both normal function and diseases at the various research levels (molecular, cellular, tissue, and organ system). Greater understanding of these sex differences will be used to steer future directions in the biomedical sciences and translational and clinical research. This review describes sex-based differences in the physiology and pathophysiology of the vasculature, with a special emphasis on sex steroid receptor (estrogen and androgen receptor) signaling and their potential impact on vascular function in health and diseases (e.g., atherosclerosis, hypertension, peripheral artery disease, abdominal aortic aneurysms, cerebral aneurysms, and stroke).

scholarly journals Cannabinoid Receptor Interacting Protein 1a (CRIP1a) in Health and Disease

Biomolecules ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 1609
Author(s):  
Emily E. Oliver ◽  
Erin K. Hughes ◽  
Meaghan K. Puckett ◽  
Rong Chen ◽  
W. Todd Lowther ◽  
...  
Keyword(s):  
Cellular Localization ◽  
Cannabinoid Receptors ◽  
Cannabinoid Receptor ◽  
Physiological Role ◽  
Interacting Protein ◽  
Cancer Subtypes ◽  
Health And Disease ◽  
Neuronal Distribution ◽  
And Function

Endocannabinoid signaling depends upon the CB1 and CB2 cannabinoid receptors, their endogenous ligands anandamide and 2-arachidonoylglycerol, and intracellular proteins that mediate responses via the C-terminal and other intracellular receptor domains. The CB1 receptor regulates and is regulated by associated G proteins predominantly of the Gi/o subtypes, β-arrestins 1 and 2, and the cannabinoid receptor-interacting protein 1a (CRIP1a). Evidence for a physiological role for CRIP1a is emerging as data regarding the cellular localization and function of CRIP1a are generated. Here we summarize the neuronal distribution and role of CRIP1a in endocannabinoid signaling, as well as discuss investigations linking CRIP1a to development, vision and hearing sensory systems, hippocampus and seizure regulation, and psychiatric disorders including schizophrenia. We also examine the genetic and epigenetic association of CRIP1a within a variety of cancer subtypes. This review provides evidence upon which to base future investigations on the function of CRIP1a in health and disease.

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.

Pharmaceutical and Biotechnological Applications of Transgenic Technology

2018 ◽  
Vol 11 (4) ◽  
pp. 4145-4153
Author(s):  
D Samba Reddy ◽  
Tina Reddy
Keyword(s):  
Mammalian Species ◽  
Genetic Diseases ◽  
Transgenic Animals ◽  
Transgenic Animal ◽  
Pharmaceutical Products ◽  
Conditional Knockout ◽  
Knock Out ◽  
Transgenic Lines ◽  
Health And Disease ◽  
Or Genes

A transgenic animal is a genetically modified species in which researchers have modified an existing gene or genes by genetic engineering techniques. Genetic modification involves the mutation, insertion, or deletion of genes. Mouse is the most widely used mammalian species for creating transgenic lines. There are two types of transgenic animals: (i) gene deleted (“knock-out”) and (ii) gene overexpressed (“knock-in”). The loss or gain of gene activity often causes changes in a mouse's phenotype, which includes appearance, behavior and other observable characteristics. Knockout mice are key animal models for studying the role of genes which have been sequenced but whose functions have not been determined.  They include constitutive knockouts (gene deleted since birth) and conditional knockout (gene turned off later after birth).  The first knockout mouse was created in 1989 by Mario Capecchi, Martin Evans, and Oliver Smithies, for which they were awarded the 2007 Nobel Prize in Physiology or Medicine.  Transgenic mouse models have revolutionized the biomedical research and provided a power tool for understanding health and disease. Transgenic animals have been created for bulk production of biotechnology and pharmaceutical products.  In 2009, the FDA approved the first human biological drug ATryn, an anticoagulant extracted from the transgenic goat's milk. The recently discovered CRISPER gene editing technology is providing new frontiers in correcting abnormal genes and hopefully provide cures for genetic diseases in the future.    

The Spectrum of Cerebrovascular Disease and Associated Cognitive Decline

2019 ◽  
pp. 574-599
Author(s):  
Victoria J. Williams ◽  
Steven E. Arnold ◽  
David H. Salat
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Cerebrovascular Disease ◽  
Cognitive Decline ◽  
Vascular Dementia ◽  
Structure And Function ◽  
Vascular Risk Factors ◽  
Vascular Health ◽  
Vascular Risk ◽  
And Function

Throughout the lifespan, common variations in systemic health and illness contribute to alterations in vasculature structure and function throughout the body, significantly increasing risk for cardiovascular and cerebrovascular disease (CVD). CVD is a prevalent cause of mortality in late life; it also promotes brain alterations, contributing to cognitive decline and, when severe, vascular dementia. Even prior to diseased states, individual variation in CVD risk is associated with structural and functional brain alterations. Yet, how cumulative asymptomatic alterations in vessel structure and function contribute to more subtle changes in brain tissue integrity and function that emerge in late life is unclear. Finally, vascular risk factors are associated with the clinical progression of neurodegenerative diseases such as Alzheimer’s disease (AD); however, recent theory posits that vascular degeneration may serve a contributory role in these conditions. This chapter reviews how lifespan changes in vascular health contribute to degenerative changes in neural tissue and the subsequent development of cognitive impairment and/or vascular dementia. It first discusses associations between vascular risk factors and cognition and also how declining vascular health may lead to cognitive impairment and dementia. Next, it identifies basic aspects of cerebrovascular anatomy and physiology sustaining tissue health and discusses how vulnerabilities of this system contribute to neurodegenerative changes. Finally, it reviews evidence of vascular contributions to AD and presents ideas for future research to better understand the full spectrum of cerebrovascular contributions to brain aging, cognitive decline, and dementia.

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