Actions of Lipoxin A4 and Related Compounds in Smooth Muscle Preparations and on the Microcirculation in Vivo

Lipoxins (LX) are lipoxygenase-derived eicosanoids with potent anti-inflammatory activities and vascular bed-dependent vasodilatory actions. LX can be formed in vitro and in vivo in a number of conditions, and we have reported that immunoreactive LXA4 (iLXA4) is physiologically excreted with human urine. Using a recently developed LX extraction method coupled to an ELISA, we examined whether iLXA4 excretion was modified by strenuous exercise, which is known to trigger potential LX-forming events. Maximal exertion significantly increased iLXA4 urinary excretion in nine healthy volunteers (0.061 ± 0.023 vs. 0.113 ± 0.057 ng/mg creatinine; P = 0.028). iLXA4 levels returned to baseline after 6 h and increased, although at a smaller extent, after 24 h. A significant correlation ( r = 0.988) was denoted between iLXA4 ELISA measurements and reversed-phase high-performance liquid chromatography quantitation of a previously described urinary tetraene, confirming its LXA4-related nature. These findings show for the first time that an increase in excretion of LXA4-related compounds can be observed in response to strenuous exercise. This may be the reflection of an enhanced LX biosynthesis, which may represent a safeguard mechanism that keeps the inflammatory reaction triggered by physical stress under control.

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In vitro desmin assembly and in vivo changes in developing smooth muscle

10.31274/rtd-180813-12384 ◽

1991 ◽

Author(s):

Rong-Ghi Robert Chou

Keyword(s):

Smooth Muscle

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Faculty Opinions recommendation of MicroRNA control of podosome formation in vascular smooth muscle cells in vivo and in vitro.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3171956.2871056 ◽

2010 ◽

Author(s):

Irina Kaverina ◽

Paul Miller

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Vascular Smooth Muscle Cells ◽

Muscle Cells

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Targeting Matrix Metalloproteinases in Atherosclerosis and Cardiovascular Dysfunction

Revista de Chimie ◽

10.37358/rc.19.2.6992 ◽

2019 ◽

Vol 70 (2) ◽

pp. 718-720

Author(s):

Lucia Corina Dima-Cozma ◽

Sebastian Cozma ◽

Delia Hinganu ◽

Cristina Mihaela Ghiciuc ◽

Florin Mitu

Keyword(s):

Smooth Muscle ◽

Matrix Metalloproteinases ◽

Cholesterol Synthesis ◽

Balloon Dilation ◽

Aortic Aneurysms ◽

Arterial Lesions ◽

Smooth Muscle Cell Migration ◽

And Migration

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.

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Inhibition of dihydropyridine-sensitive calcium entry in hypoxic relaxation of airway smooth muscle

AJP Lung Cellular and Molecular Physiology ◽

10.1152/ajplung.1995.268.2.l201 ◽

1995 ◽

Vol 268 (2) ◽

pp. L201-L206 ◽

Cited By ~ 2

Author(s):

C. Vannier ◽

T. L. Croxton ◽

L. S. Farley ◽

C. A. Hirshman

Keyword(s):

Smooth Muscle ◽

Airway Smooth Muscle ◽

Muscle Tone ◽

Bay K 8644 ◽

O2 Concentration ◽

Voltage Dependent ◽

Progressive Hypoxia ◽

Carbamyl Choline

Hypoxia dilates airways in vivo and reduces active tension of airway smooth muscle in vitro. To determine whether hypoxia impairs Ca2+ entry through voltage-dependent channels (VDC), we tested the ability of dihydropyridines to modulate hypoxia-induced relaxation of KCl- and carbamyl choline (carbachol)-contracted porcine bronchi. Carbachol- or KCl-contracted bronchial rings were exposed to progressive hypoxia in the presence or absence of 1 microM BAY K 8644 (an L-type-channel agonist). In separate experiments, rings were contracted with carbachol or KCl, treated with nifedipine (a VDC antagonist), and finally exposed to hypoxia. BAY K 8644 prevented hypoxia-induced relaxation in KCl-contracted bronchi. Nifedipine (10(-5) M) totally relaxed KCl- contracted bronchi. Carbachol-contracted bronchi were only partially relaxed by nifedipine but were completely relaxed when the O2 concentration of the gas was reduced from 95 to 0%. These data indicate that hypoxia can reduce airway smooth muscle tone by limiting entry of Ca2+ through a dihydropyridine-sensitive pathway, but that other mechanisms also contribute to hypoxia-induced relaxation of carbachol-contracted bronchi.

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Stromal cells from human long-term marrow cultures are mesenchymal cells that differentiate following a vascular smooth muscle differentiation pathway

Blood ◽

10.1182/blood.v82.1.66.bloodjournal82166 ◽

1993 ◽

Vol 82 (1) ◽

pp. 66-76 ◽

Cited By ~ 261

Author(s):

MC Galmiche ◽

VE Koteliansky ◽

J Briere ◽

P Herve ◽

P Charbord

Keyword(s):

Smooth Muscle ◽

Vascular Smooth Muscle ◽

Smooth Muscle Cells ◽

Stromal Cells ◽

Muscle Cells ◽

Mesenchymal Cells ◽

Myoid Cells ◽

Marrow Cultures

In human long-term marrow cultures connective tissue-forming stromal cells are an essential cellular component of the adherent layer where granulomonocytic progenitors are generated from week 2 onward. We have previously found that most stromal cells in confluent cultures were stained by monoclonal antibodies directed against smooth muscle- specific actin isoforms. The present study was carried out to evaluate the time course of alpha-SM-positive stromal cells and to search for other cytoskeletal proteins specific for smooth muscle cells. It was found that the expression of alpha-SM in stromal cells was time dependent. Most of the adherent spindle-shaped, vimentin-positive stromal cells observed during the first 2 weeks of culture were alpha- SM negative. On the contrary, from week 3 to week 7, most interdigitated stromal cells contained stress fibers whose backbone was made of alpha-SM-positive microfilaments. In addition, in confluent cultures, other proteins specific for smooth muscle were detected: metavinculin, h-caldesmon, smooth muscle myosin heavy chains, and calponin. This study confirms the similarity between stromal cells and smooth muscle cells. Moreover, our results reveal that cells in vivo with the phenotype closest to that of stromal cells are immature fetal smooth muscle cells and subendothelial intimal smooth muscle cells; a cell subset with limited development following birth but extensively recruited in atherosclerotic lesions. Stromal cells very probably derive from mesenchymal cells that differentiate along this distinctive vascular smooth muscle cell pathway. In humans, this differentiation seems crucial for the maintenance of granulomonopoiesis. These in vitro studies were completed by examination of trephine bone marrow biopsies from adults without hematologic abnormalities. These studies revealed the presence of alpha-SM-positive cells at diverse locations: vascular smooth muscle cells in the media of arteries and arterioles, pericytes lining capillaries, myoid cells lining sinuses at the abluminal side of endothelial cells or found within the hematopoietic logettes, and endosteal cells lining bone trabeculae. More or less mature cells of the granulocytic series were in intimate contact with the thin cytoplasmic extensions of myoid cells. Myoid cells may be the in vivo counterpart of stromal cells with the above-described vascular smooth muscle phenotype.

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Effects of Hyperglycemia on Vascular Smooth Muscle Ca2+Signaling

BioMed Research International ◽

10.1155/2017/3691349 ◽

2017 ◽

Vol 2017 ◽

pp. 1-16 ◽

Cited By ~ 6

Author(s):

Nahed El-Najjar ◽

Rashmi P. Kulkarni ◽

Nancy Nader ◽

Rawad Hodeify ◽

Khaled Machaca

Keyword(s):

Insulin Resistance ◽

Smooth Muscle ◽

Sarcoplasmic Reticulum ◽

Vascular Smooth Muscle ◽

Complex Disease ◽

Prolonged Exposure ◽

In Vitro System ◽

A7r5 Cells

Diabetes is a complex disease that is characterized with hyperglycemia, dyslipidemia, and insulin resistance. These pathologies are associated with significant cardiovascular implications that affect both the macro- and microvasculature. It is therefore important to understand the effects of various pathologies associated with diabetes on the vasculature. Here we directly test the effects of hyperglycemia on vascular smooth muscle (VSM) Ca2+signaling in an isolated in vitro system using the A7r5 rat aortic cell line as a model. We find that prolonged exposure of A7r5 cells to hyperglycemia (weeks) is associated with changes to Ca2+signaling, including most prominently an inhibition of the passive ER Ca2+leak and the sarcoplasmic reticulum Ca2+-ATPase (SERCA). To translate these findings to the in vivo condition, we used primary VSM cells from normal and diabetic subjects and find that only the inhibition of the ER Ca2+leaks replicates in cells from diabetic donors. These results show that prolonged hyperglycemia in isolation alters the Ca2+signaling machinery in VSM cells. However, these alterations are not readily translatable to the whole organism situation where alterations to the Ca2+signaling machinery are different.

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Nanonet force microscopy for measuring forces in single smooth muscle cells of the human aorta

Molecular Biology of the Cell ◽

10.1091/mbc.e17-01-0053 ◽

2017 ◽

Vol 28 (14) ◽

pp. 1894-1900 ◽

Cited By ~ 9

Author(s):

Alexander Hall ◽

Patrick Chan ◽

Kevin Sheets ◽

Matthew Apperson ◽

Christopher Delaughter ◽

...

Keyword(s):

Smooth Muscle ◽

External Perturbation ◽

Human Aorta ◽

Cycle Times ◽

Force Microscopy ◽

Cell Matrix ◽

Innovative Methods ◽

A Cell ◽

Inside Out

A number of innovative methods exist to measure cell–matrix adhesive forces, but they have yet to accurately describe and quantify the intricate interplay of a cell and its fibrous extracellular matrix (ECM). In cardiovascular pathologies, such as aortic aneurysm, new knowledge on the involvement of cell–matrix forces could lead to elucidation of disease mechanisms. To better understand this dynamics, we measured primary human aortic single smooth muscle cell (SMC) forces using nanonet force microscopy in both inside-out (I-O intrinsic contractility) and outside-in (O-I external perturbation) modes. For SMC populations, we measured the I-O and O-I forces to be 12.9 ± 1.0 and 57.9 ± 2.5 nN, respectively. Exposure of cells to oxidative stress conditions caused a force decrease of 57 and 48% in I-O and O-I modes, respectively, and an increase in migration rate by 2.5-fold. Finally, in O-I mode, we cyclically perturbed cells at constant strain of varying duration to simulate in vivo conditions of the cardiac cycle and found that I-O forces decrease with increasing duration and O-I forces decreased by half at shorter cycle times. Thus our findings highlight the need to study forces exerted and felt by cells simultaneously to comprehensively understand force modulation in cardiovascular disease.

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