scholarly journals Vascular Smooth Muscle Cell-Derived Exosomal MicroRNAs Regulate Endothelial Cell Migration Under PDGF Stimulation

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 639 ◽  
Author(s):  
Jeongyeon Heo ◽  
Hee Cheol Yang ◽  
Won Jong Rhee ◽  
Hara Kang
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Pathological Condition ◽  
Cell Communication ◽  
Endothelial Cell Migration ◽  
Vascular Cells ◽  
Vascular Pathogenesis ◽  
Pdgf Stimulation ◽  
Functional Relevance ◽  
Exosomal Mirna

Intercellular communication between vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) is essential for the maintenance of vascular homeostasis. The presence of exosomes, a recently discovered player in vascular cell communication, has been associated with vascular disease progression. However, the detailed mechanism of how the signal mediated by exosomes affects the function of vascular cells during vascular pathogenesis is yet to be further understood. In this study, we investigated the expression of exosomal microRNAs (miRNAs) secreted by VSMCs and their functional relevance to ECs in pathogenesis, including their role in processes such as platelet-derived growth factor (PDGF) stimulation. We observed that PDGF stimulation contributes to a change in exosomal miRNA release from VSMCs; specifically, miR-1246, miR-182, and miR-486 were deficient in exosomes derived from PDGF-stimulated VSMCs. The reduced miRNA expression in these exosomes is associated with an increase in EC migration. These findings increase our understanding of exosome-mediated crosstalk between vascular cells under a pathological condition.

Inhibition of vascular smooth muscle and endothelial cell migration by apolipoprotein J

2000 ◽  
Vol 191 (4) ◽  
pp. S2
Author(s):  
Nayan Sivamurthy ◽  
Darren I Rohan ◽  
David H Stone ◽  
William C Quist ◽  
Frank W LoGerfo
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Endothelial Cell ◽  
Vascular Smooth Muscle ◽  
Endothelial Cell Migration ◽  
Apolipoprotein J

Abstract 486: Artificial miRNA Based Adenoviral Adam17 Silencing Reveals Essential Role of This Metalloprotease For EGF Receptor Transactivation In Primary Cultured Vascular Smooth Muscle Cells

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Katherine Elliott ◽  
Allison Bourne ◽  
Takehiko Takayanagi ◽  
Akira Takaguri ◽  
Kunie Eguchi ◽  
...  
Keyword(s):  
Signal Transduction ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Gene Silencing ◽  
Vascular Smooth Muscle Cells ◽  
Egf Receptor ◽  
Muscle Cells ◽  
Vascular Cells ◽  
Receptor Transactivation

siRNA mediated gene silencing has been recently utilized as a powerful molecular tool to study the functional significance of a specific protein. However, due to the transient nature of silencing and insufficient transfection efficiency, this approach can be problematic in primary cell culture. To overcome such weakness of the siRNA based silencing and in order to establish reliable gene silencing in vascular cells, we devised an adenoviral-encoded miRNA based gene silencing system. Here we report the results of silencing ADAM17 in cultured rat vascular smooth muscle cells (VSMCs) and its functional consequences in angiotensin II (AngII) signal transduction. Four distinct miRNA sequences targeting rat ADAM17 were chosen based on recommendations from Invitrogen’s Block-iT RNAi Designer algorithm. The miRNA sequences were inserted into a mammalian expression vector, pcDNA 6.2-GW/EmGFP-miR, and the effective silencing by these vectors was confirmed in HEK cells expressing HA-tagged rat ADAM17. The 4 cassettes carrying the miRNAs were inserted into pAd/CMV/V5-DEST and adenoviral solutions were obtained. Greater than 95% silencing of ADAM17 was achieved when VSMC were infected with 100-200 moi of the ADAM17 miRNA encoding adeonvirus for 72 h with enhancement of infection by fugene6. Relatively linear time and concentration dependencies were observed between 1 to 3 days and 10 to 100 moi of the infection. A miR-ADAM17 (100 moi) but not miR-control (100 moi) completely inhibited 100 nM AngII-induced HB-EGF shedding in VSMCs as assessed by a reporter assay. A miR-ADAM17 but not miR-control also inhibited AngII-induced EGF receptor transactivation and subsequent ERK1/2 activation in VSMCs as assessed by immunoblotting with phospho-selective antibodies. In conclusion, ADAM17 was found to be a major sheddase for HB-EGF contributing to the growth promoting signals induced by AngII in VSMCs. An artificial miRNA-base adenoviral approach appears to be a reliable gene-silencing strategy for signal transduction research in primary cultured vascular cells.

scholarly journals Ribozyme-mediated gene knock down strategy to dissect the consequences of PDGF stimulation in vascular smooth muscle cells

2012 ◽  
Vol 5 (1) ◽  
Author(s):  
Caterina Lande ◽  
Claudia Boccardi ◽  
Lorenzo Citti ◽  
Alberto Mercatanti ◽  
Milena Rizzo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Knock Down ◽  
Pdgf Stimulation

scholarly journals Adipocytokines in Atherothrombosis: Focus on Platelets and Vascular Smooth Muscle Cells

2010 ◽  
Vol 2010 ◽  
pp. 1-26 ◽  
Author(s):  
Giovanni Anfossi ◽  
Isabella Russo ◽  
Gabriella Doronzo ◽  
Alice Pomero ◽  
Mariella Trovati
Keyword(s):  
Adipose Tissue ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Pathological Condition ◽  
Visceral Obesity ◽  
Muscle Cells ◽  
Low Grade ◽  
Endocrine Activity

Visceral obesity is a relevant pathological condition closely associated with high risk of atherosclerotic vascular disease including myocardial infarction and stroke. The increased vascular risk is related also to peculiar dysfunction in the endocrine activity of adipose tissue responsible of vascular impairment (including endothelial dysfunction), prothrombotic tendency, and low-grade chronic inflammation. In particular, increased synthesis and release of different cytokines, including interleukins and tumor necrosis factor-α(TNF-α), and adipokines—such as leptin—have been reported as associated with future cardiovascular events. Since vascular cell dysfunction plays a major role in the atherothrombotic complications in central obesity, this paper aims at focusing, in particular, on the relationship between platelets and vascular smooth muscle cells, and the impaired secretory pattern of adipose tissue.

scholarly journals Lin11-Isl1-Mec3 Domain Proteins as Mechanotransducers in Endothelial and Vascular Smooth Muscle Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Alexandra Sporkova ◽  
Subhajit Ghosh ◽  
Jaafar Al-Hasani ◽  
Markus Hecker
Keyword(s):  
Gene Expression ◽  
Blood Pressure ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Vascular Cells ◽  
Lim Domain ◽  
Cardiovascular Morbidity And Mortality

Arterial hypertension is the leading risk factor for cardiovascular morbidity and mortality worldwide. However, little is known about the cellular mechanisms underlying it. In small arteries and arterioles, a chronic increase in blood pressure raises wall tension and hence stretches, namely, the medial vascular smooth muscle cells (VSMC) but also endothelial cell (EC) to cell contacts. Initially compensated by an increase in vascular tone, the continuous biomechanical strain causes a prominent change in gene expression in both cell types, frequently driving an arterial inward remodeling process that ultimately results in a reduction in lumen diameter, stiffening of the vessel wall, and fixation of blood pressure, namely, diastolic blood pressure, at the elevated level. Sensing and propagation of this supraphysiological stretch into the nucleus of VSMC and EC therefore seems to be a crucial step in the initiation and advancement of hypertension-induced arterial remodeling. Focal adhesions (FA) represent an important interface between the extracellular matrix and Lin11-Isl1-Mec3 (LIM) domain-containing proteins, which can translocate from the FA into the nucleus where they affect gene expression. The varying biomechanical cues to which vascular cells are exposed can thus be rapidly and specifically propagated to the nucleus. Zyxin was the first protein described with such mechanotransducing properties. It comprises 3 C-terminal LIM domains, a leucine-rich nuclear export signal, and N-terminal features that support its association with the actin cytoskeleton. In the cytoplasm, zyxin promotes actin assembly and organization as well as cell motility. In EC, zyxin acts as a transcription factor, whereas in VSMC, it has a less direct effect on mechanosensitive gene expression. In terms of homology and structural features, lipoma preferred partner is the nearest relative of zyxin among the LIM domain proteins. It is almost exclusively expressed by smooth muscle cells in the adult, resides like zyxin at FA but seems to affect mechanosensitive gene expression indirectly, possibly via altering cortical actin dynamics. Here, we highlight what is currently known about the role of these LIM domain proteins in mechanosensing and transduction in vascular cells.

ROS and PDFG-β receptors are critically involved in indoxyl sulfate actions that promote vascular smooth muscle cell proliferation and migration

2009 ◽  
Vol 297 (2) ◽  
pp. C389-C396 ◽  
Author(s):  
Hidehisa Shimizu ◽  
Yuichi Hirose ◽  
Fuyuhiko Nishijima ◽  
Yoshiharu Tsubakihara ◽  
Hitoshi Miyazaki
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Nadph Oxidase ◽  
Protein Expression ◽  
Receptor Expression ◽  
Indoxyl Sulfate ◽  
Receptor Protein ◽  
Uremic Toxin ◽  
Diphenylene Iodonium ◽  
Pdgf Stimulation

Patients with chronic renal failure are at greater risk of developing atherosclerosis than healthy individuals, and recent data suggest that the putative uremic toxin indoxyl sulfate (IS) promotes the pathogenesis of atherosclerosis. The present study examined the effects of IS on vascular smooth muscle cells (VSMCs) with respect to reactive oxygen species (ROS), platelet-derived growth factor (PDGF) receptors, and mitogen-activated protein kinases (MAPKs). IS induced the migration and proliferation of VSMCs and synergistically enhanced their PDGF-induced migration as well as proliferation. The effects of PDGF were promoted after a 24-h incubation with IS despite the absence of IS during PDGF stimulation. Intracellular ROS levels were increased in the presence of IS, and PDGF-dependent ROS production was augmented by a prior 24-h incubation with IS even in the absence of IS during PDGF stimulation. These data suggest that IS increases the sensitivity of VSMCs to PDGF. IS also phosphorylated PDGF-β-receptors and upregulated PDGF-β receptor but not α-receptor protein expression in the absence of exogenous PDGF. The NADPH oxidase inhibitor diphenylene iodonium blocked IS-dependent increase in receptor expression. Administration of IS to nephrectomized rats also elevated receptor protein expression in arterial VSMCs. Inhibitors of NADPH oxidase, PDGF-β receptors, extracellular-regulated protein kinase (ERK), and p38 MAPK all inhibited IS-induced VSMCs migration and proliferation. Taken together, these findings indicate that IS induces the migration as well as proliferation of VSMCs through PDGF-β receptors and that ROS generation is critically involved in this process, which promotes the development of atherosclerosis.

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