Calcium Signaling Pathways in Smooth Muscle Remodeling During Hypertension and Asthma
Title | Calcium Signaling Pathways in Smooth Muscle Remodeling During Hypertension and Asthma PDF eBook |
Author | Martin Johnson |
Publisher | |
Pages | |
Release | 2021 |
Genre | |
ISBN |
Hypertension and asthma are highly prevalent and debilitating diseases. A common feature that has been recognized as pathogenic for these two diseases is the remodeling of the vasculature and airways. Specifically, the thickening of the smooth muscle layers of the vasculature and airways is critical for these disease processes. At the cellular level, smooth muscle cells dedifferentiate from a healthy contractile/quiescent phenotype to a highly proliferative, migratory, and secretory phenotype during vascular and airway remodeling. This phenotypic switch is also accompanied by a molecular reprogramming of the calcium (Ca2+) signaling machinery. Numerous ion channels and transporters are modulated in this dedifferentiation to favor a repertoire that spatiotemporally disseminates Ca2+ signals that activate fibroproliferative signaling at the expense of contractile function. One Ca2+ signaling pathway that reprograms during vascular and airway remodeling is the store-operated Ca2+ entry (SOCE) pathway. SOCE is initiated by depletion of the endoplasmic reticulum (ER) Ca2+ stores by receptor agonists. Upon depletion, the ER transmembrane protein, STIM, activates the plasma membrane (PM) ORAI Ca2+ channel. The activation of SOCE stimulates fibroproliferative pathways. Although not carefully studied in smooth muscle cells, the novel mitochondrial sodium (Na+)/Ca2+/Lithium (Li+) Exchanger (NCLX) has also emerged as essential for migration and proliferation for other cell types. NCLX mediates Ca2+ extrusion from the mitochondria. This dissertation illuminates how STIM1 and NCLX have critical roles in mediating smooth muscle remodeling in hypertension and asthma. We first identified L-type Ca2+ channel blockers (LCCBs), which are common antihypertensive drugs, to activate the N-terminus of STIM and stimulate vascular smooth muscle remodeling. Clinical use of LCCBs was also correlated with adverse outcomes of vascular remodeling (i.e., heart failure). In another study, we showed that STIM1 protein expression is enhanced in asthmatic airway smooth muscle (ASM). Furthermore, STIM1 was necessary for airway remodeling in asthma by stimulating pro-remodeling transcriptional reprogramming, enhancing metabolism, and activating the nuclear factor of activated T cells 4 (NFAT4) isoform. STIM1 was also crucial for airway hyperresponsiveness (AHR), possibly as a result of reduced airway remodeling (AR) and agonist-induced Ca2+ oscillations in ASM. In our final study, we further validated that NCLX regulates SOCE in ASM. Moreover, NCLX, like STIM1, is critical for regulating AR and AHR in asthma. However, NCLX mediates AR by activating pro-remodeling transcriptional reprogramming, modulation of metabolism, and the activation of Ca2+/calmodulin-dependent kinase II (CaMKII). Thus, these three critical studies further elucidate the molecular reprogramming that occurs during smooth muscle remodeling in hypertension and asthma. Furthermore, they suggest STIM and NCLX may be novel molecular targets for these diseases.
The Endothelium
Title | The Endothelium PDF eBook |
Author | Michel Félétou |
Publisher | Morgan & Claypool Publishers |
Pages | 309 |
Release | 2011 |
Genre | Science |
ISBN | 1615041230 |
The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References
Biochemistry of Smooth Muscle Contraction
Title | Biochemistry of Smooth Muscle Contraction PDF eBook |
Author | Michael Barany |
Publisher | Elsevier |
Pages | 455 |
Release | 1996-01-04 |
Genre | Science |
ISBN | 0080527892 |
This valuable resource provides a systematic account of the biochemistry of smooth muscle contraction. As a comprehensive guide to this rapidly growing area of research, it covers the structure and characteristic properties of contractile and regulatory proteins, with special emphasis on their predicted function in the live muscle. Also included in this book are intermediate filament proteins, and desmin and vimentin, whose function in smooth muscle is unknown; and several enzymes involved in the phosphorylation-dephosphorylation of contractile and other proteins.
Vascular Pharmacology: Cytoskeleton and Extracellular Matrix
Title | Vascular Pharmacology: Cytoskeleton and Extracellular Matrix PDF eBook |
Author | |
Publisher | Academic Press |
Pages | 406 |
Release | 2018-01-05 |
Genre | Medical |
ISBN | 0128121521 |
Vascular Pharmacology: Cytoskeleton and Extracellular Matrix, Volume 81, contains the latest information on the vascular cytoskeleton and extracellular matrix that is presented with helpful illustrations and supporting references by prominent scientists and highly-recognized experts in the vascular field. Topics of interest in this new release include Pharmacology of the Vascular Cytoskeleton and Extracellular Matrix, The Dynamic Actin Cytoskeleton in Smooth Muscle, The Role of the Actin Cytoskeleton in the Regulation of Vascular Inflammation, The Smoothelin Family of Proteins and the Smooth Muscle Cell Contractile Apparatus, Smooth Muscle Cytoskeletal Network Regulates Expression of the Profibrotic Genes PAI-1 and CTGF, and more. - Presents a must-read book on the vascular cytoskeleton and extracellular matrix - Contains up-to-date information on the structure, function and development of the vascular cell cytoskeleton - Includes contributors from prominent scientists and highly-recognized experts with major accomplishments in the fields of the vascular cytoskeleton, extracellular matrix, mechanotransduction and vascular remodeling
Calcium Signaling
Title | Calcium Signaling PDF eBook |
Author | Md. Shahidul Islam |
Publisher | Springer Nature |
Pages | 1110 |
Release | 2019-10-23 |
Genre | Medical |
ISBN | 3030124576 |
This volume contains a unique selection of chapters covering a wealth of contemporary topics in this ubiquitous and diverse system of cell signaling. It offers much more than the accessibility and authority of a primary text book, exploring topics ranging from the fundamental aspects of calcium signaling to its varied clinical implications. It presents comprehensive discussion of cutting-edge research alongside detailed analysis of critical issues, at the same time as setting out testable hypotheses that point the way to future scientific endeavors. The contributions feature material on theoretical and methodological topics as well as related subjects including mathematical modeling and simulations. They examine calcium signaling in a host of contexts, from mammalian cells to bacteria, fruit fly and zebrafish. With much of interest to newcomers to the field as well as seasoned experts, this new publication is both wide-ranging and authoritative. The chapter “Calcium Signaling: From Basic to Bedside” is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.
Smooth Muscle Excitation
Title | Smooth Muscle Excitation PDF eBook |
Author | T. B. Bolton |
Publisher | |
Pages | 568 |
Release | 1996 |
Genre | Medical |
ISBN |
This book is a compendium of the latest electrophysiological research on smooth muscles from an international collection of authors. It includes recent discoveries in calcium stores and their relationship to contraction and to electrical changes in the membrane. A major section of the book concentrates on calcium release mechanisms in the cell, their control, and the consequences of calcium release in the cell for membrane events. Smooth Muscle Excitation also covers the effects of chemicals released from adjacent cells. Key Features * State-of-the-art volume that represents a synopsis of all work currently being undertaken in this area throughout the world * Content covers both basic and clinical research * Provides a range of drug development studies * Presents contributions from many internationally recognized smooth muscle physiologists
How Tobacco Smoke Causes Disease
Title | How Tobacco Smoke Causes Disease PDF eBook |
Author | United States. Public Health Service. Office of the Surgeon General |
Publisher | |
Pages | 728 |
Release | 2010 |
Genre | Government publications |
ISBN |
This report considers the biological and behavioral mechanisms that may underlie the pathogenicity of tobacco smoke. Many Surgeon General's reports have considered research findings on mechanisms in assessing the biological plausibility of associations observed in epidemiologic studies. Mechanisms of disease are important because they may provide plausibility, which is one of the guideline criteria for assessing evidence on causation. This report specifically reviews the evidence on the potential mechanisms by which smoking causes diseases and considers whether a mechanism is likely to be operative in the production of human disease by tobacco smoke. This evidence is relevant to understanding how smoking causes disease, to identifying those who may be particularly susceptible, and to assessing the potential risks of tobacco products.