α2-Adrenergic receptors increase cell migration and decrease F-actin labeling in rat aortic smooth muscle cells

1998 ◽  
Vol 274 (3) ◽  
pp. C654-C662 ◽  
Author(s):  
Jeremy G. Richman ◽  
John W. Regan
Keyword(s):  
Wound Healing ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Adrenergic Receptors ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Protein Kinase Activity ◽  
Promote Cell Proliferation ◽  
Aortic Smooth Muscle

Vascular wound healing and such pathologies as atherosclerosis and restenosis are characterized by migration and proliferation of the smooth muscle cells of the media after denudation of the intima. To explore possible roles that α2-adrenergic receptors (α2-ARs) might have in these cellular responses, we characterized the α2-ARs present in explant-derived cultures of rat aortic smooth muscle (RASM) cells. The results of immunofluorescence microscopy and reverse transcription followed by the polymerase chain reaction indicated that all three α2-AR subtypes (α2A, α2B, and α2C) were initially present. Mitogen-activated protein kinase activity in the RASM cells was stimulated fivefold over basal by the α2-selective agonist dexmedetomidine (Dex) and was blocked by coincubation with the α2-selective antagonist rauwolscine (RW) or by preincubation of the cells with the Gi/Go-protein inhibitor pertussis toxin. α2-AR activation by Dex did not promote cell proliferation, as measured by the incorporation of [3H]thymidine. However, Dex significantly increased RASM cell migration, and antagonist blocked this effect. Incubation of RASM cells with Dex also produced a marked decrease in F-actin labeling, which again was prevented by coincubation with RW. The evidence clearly reveals the presence of functional α2-ARs in RASM cells. The involvement of α2-AR activation with cytoskeletal changes and cell migration is novel and indicates a potential role of these receptors in vascular wound healing and pathogenesis.

p21-activated kinase 1 participates in tracheal smooth muscle cell migration by signaling to p38 MAPK

2001 ◽  
Vol 281 (1) ◽  
pp. C123-C132 ◽  
Author(s):  
Melissa A. Dechert ◽  
Jennifer M. Holder ◽  
William T. Gerthoffer
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
P38 Mapk ◽  
Mammalian Cells ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Tracheal Smooth Muscle ◽  
Wild Type ◽  
P21 Activated Kinase

Cell migration contributes to many physiological processes and requires dynamic changes in the cytoskeleton. These migration-dependent cytoskeletal changes are partly mediated by p21-activated protein kinases (PAKs). At least four closely related isoforms, PAK1, PAK2, PAK3, and PAK4, exist in mammalian cells. In smooth muscle cells, little is known about the expression, activation, or ability of PAKs to regulate migration. Our study revealed the existence of three PAK isoforms in cultured tracheal smooth muscle cells (TSMCs). Additionally, we constructed adenoviral vectors encoding wild type and a catalytically inactive PAK1 mutant to investigate PAK activation and its role in TSMC migration. Stimulation of TSMCs with platelet-derived growth factor (PDGF) increased the activity of PAK1 over time. Overexpression of mutant PAK1 blocked PDGF-induced chemotactic cell migration. Phosphorylation of p38 mitogen-activated protein kinase (MAPK) in cells overexpressing wild-type PAK1 was similar to vector controls; however, p38 MAPK phosphorylation was severely reduced by overexpression of the PAK1 mutant. Collectively, these results suggest a role for PAK1 in chemotactic TSMC migration that involves catalytic activity and may require signaling to p38 MAPK among other pathways.

Function and role of voltage-gated sodium channel NaV1.7 expressed in aortic smooth muscle cells

2009 ◽  
Vol 296 (1) ◽  
pp. H211-H219 ◽  
Author(s):  
Kentaro Meguro ◽  
Haruko Iida ◽  
Haruhito Takano ◽  
Toshihiro Morita ◽  
Masataka Sata ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Intimal Hyperplasia ◽  
Muscle Cells ◽  
Rt Pcr ◽  
Balloon Injury ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Voltage Gated

Voltage-gated Na+ channel currents ( INa) are expressed in several types of smooth muscle cells. The purpose of this study was to evaluate the expression of INa, its functional role, pathophysiology in cultured human (hASMCs) and rabbit aortic smooth muscle cells (rASMCs), and its association with vascular intimal hyperplasia. In whole cell voltage clamp, INa was observed at potential positive to −40 mV, was blocked by tetrodotoxin (TTX), and replacing extracellular Na+ with N-methyl-d-glucamine in cultured hASMCs. In contrast to native aorta, cultured hASMCs strongly expressed SCN9A encoding NaV1.7, as determined by quantitative RT-PCR. INa was abolished by the treatment with SCN9A small-interfering (si)RNA ( P < 0.01). TTX and SCN9A siRNA significantly inhibited cell migration ( P < 0.01, respectively) and horseradish peroxidase uptake ( P < 0.01, respectively). TTX also significantly reduced the secretion of matrix metalloproteinase-2 6 and 12 h after the treatment ( P < 0.01 and P < 0.05, respectively). However, neither TTX nor siRNA had any effect on cell proliferation. L-type Ca2+ channel current was recorded, and INa was not observed in freshly isolated rASMCs, whereas TTX-sensitive INa was recorded in cultured rASMCs. Quantitative RT-PCR and immunostaining for NaV1.7 revealed the prominent expression of SCN9A in cultured rASMCs and aorta 48 h after balloon injury but not in native aorta. In conclusion, these studies show that INa is expressed in cultured and diseased conditions but not in normal aorta. The NaV1.7 plays an important role in cell migration, endocytosis, and secretion. NaV1.7 is also expressed in aorta after balloon injury, suggesting a potential role for NaV1.7 in the progression of intimal hyperplasia.

Induction of functional β-adrenergic receptors in rat aortic smooth muscle cells by sodium butyrate

1986 ◽  
Vol 35 (21) ◽  
pp. 3813-3820 ◽  
Author(s):  
Ponnal Nambi ◽  
Matthew H. Whitman ◽  
Dulcie B. Schmidt ◽  
Grace D. Heckman ◽  
Frans L. Stassen ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Sodium Butyrate ◽  
Adrenergic Receptors ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Β Adrenergic Receptors

Aging, oxidative responses, and proliferative capacity in cultured mouse aortic smooth muscle cells

2001 ◽  
Vol 280 (6) ◽  
pp. H2779-H2788 ◽  
Author(s):  
Sung-Kwon Moon ◽  
Larry J. Thompson ◽  
Nageswara Madamanchi ◽  
Scott Ballinger ◽  
John Papaconstantinou ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Muscle Cells ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Protein Kinase Activity ◽  
Proliferative Capacity ◽  
Plaque Instability ◽  
Aged Mice ◽  
Damage Accrual

The cellular mechanisms that contribute to the acceleration of atherosclerosis in aging populations are poorly understood, although it is hypothesized that changes in the proliferative capacity of vascular smooth muscle cells is contributory. We addressed the relationship among aging, generation of reactive oxygen species (ROS), and proliferation in primary culture smooth muscle cells (SMC) derived from the aortas of young (4 mo old) and aged (16 mo old) mice to understand the phenotypic modulation of these cells as aging occurs. SMC from aged mice had decreased proliferative capacity in response to α-thrombin stimulation, yet generated higher levels of ROS and had constitutively increased mitogen-activated protein kinase activity, in comparison with cells from younger mice. These effects may be explained by dysregulation of cell cycle-associated proteins such as cyclin D1 and p27Kip1 in SMC from aged mice. Increased ROS generation was associated with decreased endogenous antioxidant activity, increased lipid peroxidation, and mitochondrial DNA damage. Accrual of oxidant-induced damage and decreased proliferative capacity in SMC may explain, in part, the age-associated transition to plaque instability in humans with atherosclerosis.

Migration of cultured vascular cells in response to plasma and platelet-derived factors

1982 ◽  
Vol 56 (1) ◽  
pp. 71-82
Author(s):  
L.R. Bernstein ◽  
H. Antoniades ◽  
B.R. Zetter
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Human Platelet ◽  
Muscle Cells ◽  
Cell Types ◽  
Vascular Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

Phagokinetic migration of cultured vascular cells was tested in response to human platelet-rich serum (‘serum’) and human platelet-poor plasma serum (‘plasma’). The cell types tested included bovine aortic endothelial cells, human umbilical vein endothelial cells, human haemangiomal capillary endothelial cells, bovine adrenal microvascular pericytes, and bovine aortic smooth muscle cells. Human serum stimulated a significant increase in the rate of migration for all five cell types. Human plasma stimulated the endothelial cells to migrate but had no effect on the migration of pericytes or smooth muscle cells. Highly purified platelet-derived growth factor (PDGF) stimulated dose-dependent migration of smooth muscle cells causing a 50% increase in phagokinetic track area relative to controls. Neither pericyte nor endothelial cell migration was stimulated by PDGF. Rabbit antiserum to human PDGF completely blocked the smooth muscle cell migration induced by either 10% serum or 1 ng/ml pure PDGF. Purified platelet factor IV (PF4) stimulated migration of pericytes but not of smooth muscle cells nor endothelial cells. Sheep antiserum to human PF4 completely blocked the pericyte migration induced by either 10% serum or 1 microgram/ml pure PF4. These results indicate that PDGF is the primary factor in serum responsible for the migration of cultured aortic smooth muscle cells and that PF4 is a critical factor required to induce the migration of pericytes. Other factors present in both plasma and serum control the migration of vascular endothelial cells.

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