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In addition, it has been demonstrated that OPG is able to initiate transforming growth factor-β dependent changes in vascular smooth muscle cells, stimulating prolifactor-β dependenttion, and fibrogenesis.
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Prior work has shown that p53 protein expression is upregulated in shear-stimulated bovine aortic endothelial cells 33, in smooth muscle cells stimulated with cyclic strain 34 and in human chondrocyte explants subjected to elevated mechanical stress.
The cytosolic Ca2+ concentration ([Ca2+]c) was simultaneously measured in endothelial and smooth muscle cells stimulated with acetylcholine by confocal image of aortic slices.
Cultured human aortic endothelial and smooth muscle cells stimulated with INF-γ (an important inflammatory cytokine in AAA pathogenesis) showed decreased levels of HOXA4 protein (P < 0.0007).
Cytokines produced by inflammatory, endothelial, and smooth muscle cells stimulate migration and proliferation of VSMCs that form fibrous caps covering fatty streaks.
In this regard, PGE2 has been shown to inhibit M-CSF and GM-CSF secretion from fibroblasts or smooth muscle cells stimulated with inflammatory cytokines [33,34].
Additionally, pyrogallol decreased isolated myocyte cytosolic calcium utilization by 54% in muscle cells stimulated with bethanechol (10 μM) (KRB: 442.7 ± 98.90 vs 203.1 ± 5.83 nM, n = 3).
In Wang et al's group, 4OGOMV was proven to be able to inhibit the proliferation of smooth muscle cells stimulated by TNF-α in a smooth muscle cell culture [ 27].
Our approach of using primary cells to examine the transcriptomic responses of muscle cells stimulated with IL-1β avoids complex host and cell type responses observed during in vivo experiments.
In vascular smooth muscle cells stimulated by vasoactive agents, rho undergoes GDP-GTP exchange to become activated with a subsequent translocation to the cell membrane where it interacts with its downstream effectors such as rho-kinase (ROCK).
Thus, except in cases of very severe disease, IL-6 production appears to be activated in vitro (muscle cells stimulated with anti-AChR antibodies) and ex vivo (IL-6 protein in human MG muscle and IL-6 mRNA in mouse muscle).
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