The Experts below are selected from a list of 202755 Experts worldwide ranked by ideXlab platform
Marc B Hershenson - One of the best experts on this subject based on the ideXlab platform.
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airway Smooth Muscle in asthma
Annual Review of Pathology-mechanisms of Disease, 2008Co-Authors: Marc B Hershenson, Melanie Brown, Blanca Camorettimercado, Julian SolwayAbstract:Airway Smooth Muscle plays a multifaceted role in the pathogenesis of asthma. We review the current understanding of the contribution of airway myocytes to airway inflammation, airway wall remodeling, and airflow obstruction in this prevalent disease syndrome. Together, these roles make airway Smooth Muscle an attractive target for asthma therapy.
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airway Smooth Muscle growth in asthma proliferation hypertrophy and migration
Proceedings of the American Thoracic Society, 2008Co-Authors: Kelley J Bentley, Marc B HershensonAbstract:Increased airway Smooth Muscle mass is present in fatal and non-fatal asthma. However, little information is available regarding the cellular mechanism (i.e., hyperplasia vs. hypertrophy). Even less information exists regarding the functional consequences of airway Smooth Muscle remodeling. It would appear that increased airway Smooth Muscle mass would tend to increase airway narrowing and airflow obstruction. However, the precise effects of increased airway Smooth Muscle mass on airway narrowing are not known. This review will consider the evidence for airway Smooth Muscle cell proliferation and hypertrophy in asthma, potential functional effects, and biochemical mechanisms.
Andrew J. Halayko - One of the best experts on this subject based on the ideXlab platform.
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microrna expression in human airway Smooth Muscle cells role of mir 25 in regulation of airway Smooth Muscle phenotype
American Journal of Respiratory Cell and Molecular Biology, 2010Co-Authors: Andrew R Kuhn, William T Gerthoffer, Andrew J. Halayko, Karen Schlauch, Ronna Lao, Cherie A SingerAbstract:Defining mechanisms by which differentiated, contractile Smooth Muscle cells become proliferative and secretory in response to mechanical and environmental stress is crucial for determining the contribution of airway Smooth Muscle (ASM) to inflammatory responses that result in airway disease. Regulation by microRNAs (miRNAs) has emerged as an important post-transcriptional mechanism regulating gene expression that may modulate ASM phenotype, but little is known about the expression and functions of miRNA in Smooth Muscle. In the present study we used microarrays to determine whether miRNAs in human ASM cells are altered by a proinflammatory stimulus. In ASM cells exposed to IL-1β, TNF-α, and IFN-γ, we found 11 miRNAs to be significantly down-regulated. We verified decreased expression of miR-25, miR-140*, mir-188, and miR-320 by quantitative PCR. Analysis of miR-25 expression indicates that it has a broad role in regulating ASM phenotype by modulating expression of inflammatory mediators such as RANTES, e...
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Airway Smooth Muscle phenotype and function: interactions with current asthma therapies.
Current drug targets, 2006Co-Authors: Andrew J. Halayko, Thai Tran, Akira Yamasaki, Reinoud GosensAbstract:Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of Smooth Muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway Smooth Muscle spasm. A hallmark diagnostic symptom of asthma is airway hyperresponsiveness to inhaled non-allergic stimuli, such as methacholine, that directly induce airway Smooth Muscle contraction. Inhaled gluccocorticoids are used for first-line prevention of airway inflammation, and are frequently combined with inhaled beta2-adrenoceptor agonists that can effectively relax airway Smooth Muscle and restore airway conductance. Leukotriene receptor antagonists and anti-cholinergics can also be used in many patients to ensure optimal control of symptoms. With increasing disease duration irreversible airway restriction develops from inflammation-driven fibro-proliferative airway remodeling that includes increased deposition of extracellular matrix, the accumulation of airway Smooth Muscle, and increased numbers of myofibroblasts. Mature airway Smooth Muscle cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory functional responses that contribute to airway remodeling and persistent hyperresponsiveness. This review assesses current understanding of acute and chronic effects of common anti-asthma medications on the diverse phenotype and functional characteristics of airway Smooth Muscle cells. Furthermore, we describe the significance of these effects in the treatment of asthma symptoms and pathogenesis.
Frank V Brozovich - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of vascular Smooth Muscle contraction and the basis for pharmacologic treatment of Smooth Muscle disorders
Pharmacological Reviews, 2016Co-Authors: Frank V Brozovich, Christopher Nicholson, Chantal V Degen, Milan Aggarwal, Kathleen G MorganAbstract:The Smooth Muscle cell directly drives the contraction of the vascular wall and hence regulates the size of the blood vessel lumen. We review here the current understanding of the molecular mechanisms by which agonists, therapeutics, and diseases regulate contractility of the vascular Smooth Muscle cell and we place this within the context of whole body function. We also discuss the implications for personalized medicine and highlight specific potential target molecules that may provide opportunities for the future development of new therapeutics to regulate vascular function.
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nonMuscle myosin is regulated during Smooth Muscle contraction
American Journal of Physiology-heart and Circulatory Physiology, 2009Co-Authors: Samantha Yuen, Ozgur Ogut, Frank V BrozovichAbstract:The participation of nonMuscle myosin in force maintenance is controversial. Furthermore, its regulation is difficult to examine in a cellular context, as the light chains of Smooth Muscle and nonMuscle myosin comigrate under native and denaturing electrophoresis techniques. Therefore, the regulatory light chains of Smooth Muscle myosin (SM-RLC) and nonMuscle myosin (NM-RLC) were purified, and these proteins were resolved by isoelectric focusing. Using this method, intact mouse aortic Smooth Muscle homogenates demonstrated four distinct RLC isoelectric variants. These spots were identified as phosphorylated NM-RLC (most acidic), nonphosphorylated NM-RLC, phosphorylated SM-RLC, and nonphosphorylated SM-RLC (most basic). During Smooth Muscle activation, NM-RLC phosphorylation increased. During depolarization, the increase in NM-RLC phosphorylation was unaffected by inhibition of either Rho kinase or PKC. However, inhibition of Rho kinase blocked the angiotensin II-induced increase in NM-RLC phosphorylation. Additionally, force for angiotensin II stimulation of aortic Smooth Muscle from heterozygous nonMuscle myosin IIB knockout mice was significantly less than that of wild-type littermates, suggesting that, in Smooth Muscle, activation of nonMuscle myosin is important for force maintenance. The data also demonstrate that, in Smooth Muscle, the activation of nonMuscle myosin is regulated by Ca2+-calmodulin-activated myosin light chain kinase during depolarization and a Rho kinase-dependent pathway during agonist stimulation.
Reinoud Gosens - One of the best experts on this subject based on the ideXlab platform.
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Airway Smooth Muscle phenotype and function: interactions with current asthma therapies.
Current drug targets, 2006Co-Authors: Andrew J. Halayko, Thai Tran, Akira Yamasaki, Reinoud GosensAbstract:Asthma incidence has climbed markedly in the past two decades despite an increased use of medications that suppress airway inflammation and repress contraction of Smooth Muscle that encircles the airways. Asthmatics exhibit episodes of airway inflammation that potentiates reversible airway Smooth Muscle spasm. A hallmark diagnostic symptom of asthma is airway hyperresponsiveness to inhaled non-allergic stimuli, such as methacholine, that directly induce airway Smooth Muscle contraction. Inhaled gluccocorticoids are used for first-line prevention of airway inflammation, and are frequently combined with inhaled beta2-adrenoceptor agonists that can effectively relax airway Smooth Muscle and restore airway conductance. Leukotriene receptor antagonists and anti-cholinergics can also be used in many patients to ensure optimal control of symptoms. With increasing disease duration irreversible airway restriction develops from inflammation-driven fibro-proliferative airway remodeling that includes increased deposition of extracellular matrix, the accumulation of airway Smooth Muscle, and increased numbers of myofibroblasts. Mature airway Smooth Muscle cells are phenotypically plastic, enabling them to subserve contractile, proliferative, migratory and secretory functional responses that contribute to airway remodeling and persistent hyperresponsiveness. This review assesses current understanding of acute and chronic effects of common anti-asthma medications on the diverse phenotype and functional characteristics of airway Smooth Muscle cells. Furthermore, we describe the significance of these effects in the treatment of asthma symptoms and pathogenesis.
Sander S Rensen - One of the best experts on this subject based on the ideXlab platform.
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regulation and characteristics of vascular Smooth Muscle cell phenotypic diversity
Netherlands Heart Journal, 2007Co-Authors: Sander S Rensen, Pieter A Doevendans, G J J M Van EysAbstract:Vascular Smooth Muscle cells can perform both contractile and synthetic functions, which are associated with and characterised by changes in morphology, proliferation and migration rates, and the expression of different marker proteins. The resulting phenotypic diversity of Smooth Muscle cells appears to be a function of innate genetic programmes and environmental cues, which include biochemical factors, extracellular matrix components, and physical factors such as stretch and shear stress. Because of the diversity among Smooth Muscle cells, blood vessels attain the flexibility that is necessary to perform efficiently under different physiological and pathological conditions. In this review, we discuss recent literature demonstrating the extent and nature of Smooth Muscle cell diversity in the vascular wall and address the factors that affect Smooth Muscle cell phenotype. (Neth Heart J 2007;15:100-8.)
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Smoothelin in vascular Smooth Muscle cells
Trends in cardiovascular medicine, 2007Co-Authors: G J J M Van Eys, Petra Niessen, Sander S RensenAbstract:Smoothelin-A and -B have only been found in fully differentiated contractile Smooth Muscle cells. They are increasingly used to monitor the Smooth Muscle cell differentiation process to a contractile or synthetic phenotype. Vascular-specific Smoothelin-B is the first Smooth Muscle cell marker that disappears when vascular tissues are compromised, for example, in atherosclerosis or restenosis. Recently obtained data show that Smoothelin deficiency results in a considerable loss of contractile potential and hence in impaired Smooth Muscle function and suggest that Smoothelins are part of the contractile apparatus.