Mechanisms regulating the vascular smooth muscle Na/H exchanger (NHE-1) in diabetes

1998 ◽  
Vol 76 (5) ◽  
pp. 751-759 ◽  
Author(s):  
Katherine M Hannan ◽  
Peter J Little
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Hydrogen Exchange ◽  
Muscle Cells ◽  
Cell Types ◽  
Sodium Hydrogen ◽  
Sodium Hydrogen Exchanger ◽  
Multiple Cell

Vascular disease is a major component of the complications associated with diabetes. The pathology involves hypertrophy and proliferation of vascular smooth muscle cells and the production and modification of extracellular matrix. The sodium/hydrogen exchanger has been widely implicated in the growth of multiple cell types, including vascular smooth muscle. Increases in sodium/hydrogen exchange activity serve as an effector or at least as an indicator of vascular activation. This article is concerned with the role of the biochemical abnormalities of diabetes exerting their pathological effects on vascular smooth muscle cells via altering sodium/hydrogen exchange activity.Key words: diabetes, sodium/hydrogen exchanger, vascular smooth muscle, complications.

scholarly journals Spatially selective myosin regulatory light chain regulation is absent in dedifferentiated vascular smooth muscle cells but is partially induced by fibronectin and Klf4

2019 ◽  
Vol 316 (4) ◽  
pp. C509-C521 ◽  
Author(s):  
Tsubasa S. Matsui ◽  
Shinji Deguchi
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Light Chain ◽  
Muscle Cells ◽  
Cell Types ◽  
Myosin Regulatory Light Chain ◽  
Phosphorylation State ◽  
Spatial Regulation

The phosphorylation state of myosin regulatory light chain (MRLC) is central to the regulation of contractility that impacts cellular homeostasis and fate decisions. Rho-kinase (ROCK) and myosin light chain kinase (MLCK) are major kinases for MRLC documented to selectively regulate MRLC in a subcellular position-specific manner; specifically, MLCK in some nonmuscle cell types works in the cell periphery to promote migration, while ROCK does so at the central region to sustain contractility. However, it remains unclear whether or not the spatially selective regulation of the MRLC kinases is universally present in other cell types, including dedifferentiated vascular smooth muscle cells (SMCs). Here, we demonstrate the absence of the spatial regulation in dedifferentiated SMCs using both cell lines and primary cells. Thus, our work is distinct from previous reports on cells with migratory potential. We also observed that the spatial regulation is partly induced upon fibronectin stimulation and Krüppel-like factor 4 overexpression. To find clues to the mechanism, we reveal how the phosphorylation state of MRLC is determined within dedifferentiated A7r5 SMCs under the enzymatic competition among three major regulators ROCK, MLCK, and MRLC phosphatase (MLCP). We show that ROCK, but not MLCK, predominantly regulates the MRLC phosphorylation in a manner distinct from previous in vitro-based and in silico-based reports. In this ROCK-dominating cellular system, the contractility at physiological conditions was regulated at the level of MRLC diphosphorylation, because its monophosphorylation is already saturated. Thus, the present study provides insights into the molecular basis underlying the absence of spatial MRLC regulation in dedifferentiated SMCs.

Regulation of calcium-activated chloride channels in smooth muscle cells: a complex picture is emerging

2005 ◽  
Vol 83 (7) ◽  
pp. 541-556 ◽  
Author(s):  
Normand Leblanc ◽  
Jonathan Ledoux ◽  
Sohag Saleh ◽  
Amy Sanguinetti ◽  
Jeff Angermann ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Chloride Channels ◽  
Muscle Cells ◽  
Cell Types ◽  
Dependent Protein Kinase ◽  
Intracellular Ca ◽  
Dependent Protein

Calcium-activated chloride channels (ClCa) are ligand-gated anion channels as they have been shown to be activated by a rise in intracellular Ca2+ concentration in various cell types including cardiac, skeletal and vascular smooth muscle cells, endothelial and epithelial cells, as well as neurons. Because ClCa channels are normally closed at resting, free intracellular Ca2+ concentration (~100 nmol/L) in most cell types, they have generally been considered excitatory in nature, providing a triggering mechanism during signal transduction for membrane excitability, osmotic balance, transepithelial chloride movements, or fluid secretion. Unfortunately, the genes responsible for encoding this class of ion channels is still unknown. This review centers primarily on recent findings on the properties of these channels in smooth muscle cells. The first section discusses the functional significance and biophysical and pharmacological properties of ClCa channels in smooth muscle cells, and ends with a description of 2 candidate gene families (i.e., CLCA and Bestrophin) that are postulated to encode for these channels in various cell types. The second section provides a summary of recent findings demonstrating the regulation of native ClCa channels in vascular smooth muscle cells by calmodulin-dependent protein kinase II and calcineurin and how their fine tuning by these enzymes may influence vascular tone. Key words: calcium-activated chloride channels, vascular smooth muscle cells, ion channels, calmodulin-dependent protein kinase II, calcineurin

Neuropeptide Y (NPY) and NPY receptors in the cardiovascular system: implication in the regulation of intracellular calciumThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigators' Forum.

2007 ◽  
Vol 85 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Danielle Jacques ◽  
Dima Abdel-Samad
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Neuropeptide Y ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Heart Cells ◽  
Microscopy Technique ◽  
Intracellular Ca

The 3-dimensional confocal microscopy technique has allowed us to identify the presence of yet another cardioactive factor and its receptor, namely neuropeptide Y (NPY) and its Y1 receptor, at the level of vascular smooth muscle cells and heart cells including endocardial endothelial cells (EECs). Using this technique, we also demonstrated that NPY is able to induce an increase in both cytosolic and nuclear calcium in all these cell types. Furthermore, besides being expressed at the level of EECs, NPY is also released from these cells following a sustained increase of intracellular Ca2+. This suggests the ability of NPY to contribute to the regulation of the excitation–secretion coupling of EECs and the excitation–contraction coupling of cardiomyocytes and vascular smooth muscle cells.

Abstract 573: Vibrational Spectroscopy Discriminates Differentiated Vascular Smooth Muscle Cells From Mesenchymal Stem Cells and Their Vascular Progeny

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Claire Molony ◽  
Mariana Di Luca ◽  
Jennifer McIntyre ◽  
Bryan Hennelly ◽  
Hugh J Byrne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vibrational Spectroscopy ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Linear Discriminant

Background: The source of intimal vascular smooth muscle cells (SMCs) following vascular remodelling has been controversial, with either de-differentiated SMCs and/or stem cell-derived SMCs playing a putative role. Fourier transform Infrared (FTIR) and Raman spectroscopy are complementary forms of vibrational spectroscopy which provide an excellent platform for extracting important biochemical data in a label-free manner to discriminate cell types. Aim: Determine whether native differentiated SMCs can be distinguished from mesenchymal stem cells (MSCs) and MSC-derived SMCs using vibrational spectroscopy. Methods: Freshly isolated rat aortic differentiated SMCs (up to passage 4), CD44+ bone marrow derived mesenchymal stem cells (MSCs), MSC-derived smooth muscle cells (mdSMCs - after TGF-β1 treatment for 14 d) and osteoblasts (mdOSTs - after osteogenic inductive stimulation for 21 d) were grown and fixed on calcium fluoride slides before their respective spectra were recorded by Raman and FTIR Spectroscopy. Multivariate statistical algorithms, including Principal Components Analysis (PCA) and Linear Discriminant Analysis (LDA), were applied to the spectra in order to classify the cell types based on their biochemical variation. Results: The recorded spectra for each cell type revealed significant visible differences between the cells across all recordings. The PCA score plot discriminated the cells based on their unique characteristics. A combination of PCA-LDA were applied for classification, and a leave one out cross validation resulted in sensitivities and specificities that were >95%. Conclusion: Vibrational spectroscopy discriminates differentiated SMCs from MSC and their vascular progeny and may be useful for identifying these cells as early biomarkers of disease.

scholarly journals Hexamethylenebisacetamide selectively inhibits the proliferation of human and rat vascular smooth-muscle cells

1992 ◽  
Vol 283 (2) ◽  
pp. 403-408 ◽  
Author(s):  
D J Grainger ◽  
T R Hesketh ◽  
P L Weissberg ◽  
J C Metcalfe
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Maximal Inhibition ◽  
Vsmc Proliferation ◽  
Adp Ribosyltransferase

Hexamethylenebisacetamide (HMBA) selectively and reversibly inhibited proliferation of human and rat vascular smooth-muscle cells (VSMCs) compared with endothelial cells, fibroblasts or lymphocytes. Half-maximal inhibition of VSMC proliferation occurred at 2-5 mM-HMBA, and at 30- greater than 50 mM for other cell types. HMBA also prevented de-differentiation, defined by the loss of smooth-muscle-specific myosin heavy chain, of primary rat VSMCs and caused partial re-differentiation of subcultured cells. Other inhibitors of ADP-ribosyltransferase were also selective inhibitors of VSMC proliferation.

scholarly journals Activation of K+ channels induces apoptosis in vascular smooth muscle cells

2001 ◽  
Vol 280 (4) ◽  
pp. C970-C979 ◽  
Author(s):  
Stefanie Krick ◽  
Oleksandr Platoshyn ◽  
Michele Sweeney ◽  
Hyong Kim ◽  
Jason X.-J. Yuan
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Ion Homeostasis ◽  
Muscle Cells ◽  
Cell Types ◽  
K Channel ◽  
K Channels ◽  
Induced Apoptosis

Intracellular K+ plays an important role in controlling the cytoplasmic ion homeostasis for maintaining cell volume and inhibiting apoptotic enzymes in the cytosol and nucleus. Cytoplasmic K+ concentration is mainly regulated by K+ uptake via Na+-K+-ATPase and K+ efflux through K+ channels in the plasma membrane. Carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore that dissipates the H+ gradient across the inner membrane of mitochondria, induces apoptosis in many cell types. In rat and human pulmonary artery smooth muscle cells (PASMC), FCCP opened the large-conductance, voltage- and Ca2+-sensitive K+ (maxi-K) channels, increased K+ currents through maxi-K channels [ I K(Ca)], and induced apoptosis. Tetraethylammonia (1 mM) and iberiotoxin (100 nM) decreased I K(Ca) by blocking the sarcolemmal maxi-K channels and inhibited the FCCP-induced apoptosis in PASMC cultured in media containing serum and growth factors. Furthermore, inhibition of K+ efflux by raising extracellular K+ concentration from 5 to 40 mM also attenuated PASMC apoptosis induced by FCCP and the K+ ionophore valinomycin. These results suggest that FCCP-mediated apoptosis in PASMC is partially due to an increase of maxi-K channel activity. The resultant K+ loss through opened maxi-K channels may serve as a trigger for cell shrinkage and caspase activation, which are major characteristics of apoptosis in pulmonary vascular smooth muscle cells.

scholarly journals Phenotypic Modulation of Macrophages and Vascular Smooth Muscle Cells in Atherosclerosis—Nitro-Redox Interconnections

Antioxidants ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 516
Author(s):  
Justine Bonetti ◽  
Alessandro Corti ◽  
Lucie Lerouge ◽  
Alfonso Pompella ◽  
Caroline Gaucher
Keyword(s):  
Oxidative Stress ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Local Environment ◽  
Muscle Cells ◽  
Cell Types ◽  
Atherosclerosis Development ◽  
Underlying Mechanisms

Monocytes/macrophages and vascular smooth muscle cells (vSMCs) are the main cell types implicated in atherosclerosis development, and unlike other mature cell types, both retain a remarkable plasticity. In mature vessels, differentiated vSMCs control the vascular tone and the blood pressure. In response to vascular injury and modifications of the local environment (inflammation, oxidative stress), vSMCs switch from a contractile to a secretory phenotype and also display macrophagic markers expression and a macrophagic behaviour. Endothelial dysfunction promotes adhesion to the endothelium of monocytes, which infiltrate the sub-endothelium and differentiate into macrophages. The latter become polarised into M1 (pro-inflammatory), M2 (anti-inflammatory) or Mox macrophages (oxidative stress phenotype). Both monocyte-derived macrophages and macrophage-like vSMCs are able to internalise and accumulate oxLDL, leading to formation of “foam cells” within atherosclerotic plaques. Variations in the levels of nitric oxide (NO) can affect several of the molecular pathways implicated in the described phenomena. Elucidation of the underlying mechanisms could help to identify novel specific therapeutic targets, but to date much remains to be explored. The present article is an overview of the different factors and signalling pathways implicated in plaque formation and of the effects of NO on the molecular steps of the phenotypic switch of macrophages and vSMCs.

scholarly journals Inducing highly physiologically relevant phenotypes of human vascular smooth muscle cells via 3D printing

2020 ◽  
Author(s):  
Peiran Zhu ◽  
Xuzhao Li ◽  
Wang Xin ◽  
Menglin Wang ◽  
Chengzhen Yin ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Geometrical Constraints ◽  
3D Printed ◽  
Morphological Phenotype

ABSTRACTVascular smooth muscle cells (vSMCs) are one of the essential cell types in blood vessel walls. A significant vSMC phenotype characteristic is that they collectively wrap around the outer layer of the healthy blood vessels with spindle-like morphology and help maintain the vascular tones and regulate the blood flow. Both physiological and biomedical research are impeded by the standard 2D cell culture approaches which do not create in vivo like microenvironment. Here, we systematically investigated the vSMCs culturing within 3D printed geometrical constraints and on printed microfilaments. Based on these models, we demonstrate a simple bioprinting approach for fast manufacturing vessel architectures with micro-grooved surfaces for vSMCs alignment. We validated that the vSMCs cultured on the printed vessel with microfilaments (VWMF) present a more physiologically relevant morphological phenotype and gene expression profile, and they are considerably more active in wound healing and ischemia than conventional planarly cultured vSMCs.

Serotonin increases DNA synthesis in rat proximal and distal pulmonary vascular smooth muscle cells in culture

1994 ◽  
Vol 266 (2) ◽  
pp. L178-L186 ◽  
Author(s):  
B. R. Pitt ◽  
W. Weng ◽  
A. R. Steve ◽  
R. D. Blakely ◽  
I. Reynolds ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Dna Synthesis ◽  
Receptor Antagonist ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cell Types ◽  
Calcium Transients ◽  
Thymidine Uptake

Cultured smooth muscle cells obtained from rat lung periphery (RPC) and proximal pulmonary artery (RSMC) expressed mRNA for serotonin (5-HT) type 2 receptor (5-HT2) and 5-HT transporter (by Northern blot analysis). Functional expression of these genes was evident since both cell types 1) bound 125I-labeled lysergic acid diethylamide (LSD; 5-HT2 receptor antagonist) that was equally effectively displaced by either ketanserin or mianserin; and 2) transported 5-[3H]HT in an imipramine-sensitive manner. Serotonin (10(-9)-10(-5) M) stimulated DNA synthesis (as measured by [3H]thymidine uptake) in RPC and RSMC. The 5-HT-induced increase in DNA synthesis was significantly inhibited in both cell types by the 5-HT2 receptor antagonist, ketanserin (10(-7)-10(-6) M), and by fluoxetine (10(-6) M), a putative 5-HT transport inhibitor. Acute exposure to 5-HT (1–100 microM) caused an abrupt rise in intracellular calcium ([Ca2+]i) in single pulmonary vascular smooth muscle cells as microspectrofluorometrically determined using the calcium-sensitive dye, fura 2. The 5-HT-induced change in [Ca2+]i was completely abolished in the presence of 10(-6) M ketanserin as well as imipramine or fluoxetine (10(-6) M). The calcium transients due to 5-HT persisted in a Na(+)-free condition (in which the transporter activity was completely abolished) and imipramine and fluoxetine (and ketanserin) were effective inhibitors of 5-HT under these conditions. Therefore, the 5-HT2 receptor, but not the transporter, is responsible for initiating the acute effects (e.g., calcium transients) of 5-HT in cultured rat pulmonary vascular smooth muscle cells and fluoxetine (1 microM) may have 5-HT2-receptor antagonist properties.(ABSTRACT TRUNCATED AT 250 WORDS)

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