Overexpression of Tissue Factor Pathway Inhibitor in Aortic Smooth Muscle Cells Inhibits Cell Migration Induced by Tissue Factor/Factor VIIa Complex

1999 ◽  
Vol 94 (6) ◽  
pp. 401-406 ◽  
Author(s):  
Yuichiro Sato ◽  
Hiroaki Kataoka ◽  
Yujiro Asada ◽  
Kousuke Marutsuka ◽  
Yu-ichi Kamikubo ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Tissue Factor Pathway Inhibitor ◽  
Factor Viia ◽  
Muscle Cells ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle ◽  
Tissue Factor Pathway

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.

Regulation of Tissue Factor Pathway Inhibitor Expression in Smooth Muscle Cells

Blood ◽  
1999 ◽  
Vol 94 (2) ◽  
pp. 579-586 ◽  
Author(s):  
Usha R. Pendurthi ◽  
L. Vijaya Mohan Rao ◽  
J. Todd Williams ◽  
Steven Idell
Keyword(s):  
Smooth Muscle ◽  
Growth Factor ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Blot Analysis ◽  
Tissue Factor Pathway Inhibitor ◽  
Muscle Cells ◽  
Conditioned Media ◽  
Tissue Factor Pathway

Tissue factor pathway inhibitor (TFPI) is the primary physiological inhibitor that regulates tissue factor-induced blood coagulation. TFPI is thought to be synthesized, in vivo, primarily by microvascular endothelial cells. Little is known about how TFPI is regulated under pathophysiological conditions. In this study, we determined mechanisms by which TFPI expression is regulated by human pulmonary artery smooth muscle cells (PASMC), because these cells contribute to remodeling of the pulmonary vasculature in disease. PASMC in culture constitutively synthesize and secrete TFPI. Exposure of PASMC to phorbol myristate acetate, lipopolysaccharide, tumor necrosis factor , thrombin, interleukin-1, and transforming growth factor-β had no significant effect on expression of TFPI by PASMC. By contrast, treatment of PASMC with serum and basic fibroblast growth factor (bFGF)/heparin markedly upregulated the expression of TFPI activity and antigen. On Western blot analysis, a protein consistent with full-length TFPI (42 kD) was identified in the conditioned media of PASMC, and the levels of the protein were much higher in the conditioned media of serum and bFGF/heparin-treated cells. Northern blot analysis showed that PASMC constitutively express TFPI mRNA, and treatment of cells with serum and bFGF/heparin had a minimal effect on the steady-state levels of TFPI mRNA. Nuclear run-on analysis did not show a significant increase in the transcriptional rate of TFPI gene in PASMC treated with serum or bFGF/heparin. Cycloheximide, but not actinomycin-D, treatment inhibited the serum and bFGF/heparin-induced increase in TFPI activity in PASMC. In conclusion, our data demonstrate that PASMC constitutively synthesize and secrete TFPI and serum or bFGF upregulate its expression, suggesting that growth factors that can stimulate the vessel wall in vivo might locally regulate TFPI expression. Our study also suggests that control of TFPI expression by serum or bFGF occurs via translational rather than transcriptional regulation.

scholarly journals Expression of Tissue Factor Pathway Inhibitor in Vascular Smooth Muscle Cells and Its Regulation by Growth Factors

1998 ◽  
Vol 83 (12) ◽  
pp. 1264-1270 ◽  
Author(s):  
Noel M. Caplice ◽  
Cheryl S. Mueske ◽  
Laurel S. Kleppe ◽  
Timothy E. Peterson ◽  
George J. Broze ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Growth Factors ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Vascular Smooth Muscle Cells ◽  
Tissue Factor Pathway Inhibitor ◽  
Muscle Cells ◽  
Tissue Factor Pathway

Modulation of tissue factor expression by rapamycin and FK-506 in lipopolysaccharide-stimulated human mononuclear cells and serum-stimulated aortic smooth muscle cells

2005 ◽  
Vol 94 (07) ◽  
pp. 46-52 ◽  
Author(s):  
Soumeya Hammal ◽  
Nejma Ameziane ◽  
Marie-Thérèse Labro ◽  
Dominique de Prost ◽  
Véronique Ollivier
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Mrna Expression ◽  
Tissue Factor ◽  
Mononuclear Cells ◽  
Muscle Cells ◽  
Monocytic Cells ◽  
Fk 506 ◽  
Aortic Smooth Muscle Cells ◽  
Aortic Smooth Muscle

SummaryInflammation is a key pathogenic component of atherosclerosis; it also promotes thrombosis, a process underlying acute coronary events and stroke. Cells present in atherosclerotic plaque show abnormal tissue factor (TF) expression. Macrolides, in addition to their antimicrobial properties, have antiinflammatory effects that might help prevent atherothrombosis. The aim of this study was to determine the effect of an immunosuppressant macrolide, rapamycin (Sirolimus), on the expression of TF and its inhibitor (TFPI) by monocytic cells (human blood mononuclear and THP-1 cells) and human aortic smooth muscle cells, in comparison with FK-506 and azithromycin. In monocytic cells, rapamycin and FK-506 inhibited LPS-induced TF activity, antigen and mRNA expression through a transcriptional mechanism involving NF-κB. In smooth muscle cells, rapamycin and azithromycin had no effect on serum-induced TF expression, while FK-506 increased serum-induced TF protein and mRNA expression. TFPI levels in the culture supernatants of serum-stimulated smooth muscle cells were not modified by any of the three macrolides. Rapamycin slightly inhibits TFPI induction by LPS in monocytic cells. In addition to its recently established efficacy in the prevention of stent restenosis, the inhibitory effect of rapamycin on theTF pathway might have interesting therapeutic implications.

Synthesis and Expression of Tissue Factor Pathway Inhibitor by Serum-stimulated Fibroblasts, Vascular Smooth Muscle Cells and Cardiac Myocytes

1999 ◽  
Vol 82 (12) ◽  
pp. 1663-1672 ◽  
Author(s):  
S. Steer ◽  
M. N. Kuppuswamy ◽  
W. Kisiel ◽  
S. P. Bajaj ◽  
M. S. Bajaj
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Tissue Factor ◽  
Cardiac Myocytes ◽  
Vascular Smooth Muscle Cells ◽  
Tissue Factor Pathway Inhibitor ◽  
Muscle Cells ◽  
Serum Stimulation ◽  
Tissue Factor Pathway

SummaryTissue factor pathway inhibitor (TFPI) plays an important role in regulating tissue factor (TF)-initiated blood coagulation. Since serum stimulation of fibroblasts, vascular smooth muscle cells and cardiac myocytes in culture increases the expression of TF mRNA and antigen (Ag) in these cells, we hypothesized that serum may also induce increased synthesis of TFPI in these cells to regulate the TF-induced extravascular clotting at an injury site. To test this concept, we used primary isolates of the following human cell types – fetal and adult lung fibroblasts, pulmonary and aortic smooth muscle cells, and cardiac myocytes. Serum-stimulation of these cells resulted in an increased expression of TF mRNA and Ag (8 to10-fold). Upon serum stimulation, expression of TFPI mRNA and Ag was also increased in these cells. However, the increase in TFPI-Ag (6 to 8-fold) was significantly greater than the TFPI mRNA (2 to 3-fold). Notably, increased expression of TFPI persisted after the TF expression had declined. Further, increased synthesis of TFPI initially led to the saturation of heparin-releasable binding sites. TFPI-Ag was detected by Western blotting, 35S-metabolic labeling and activity assays on the conditioned media, heparin-released material from cells, and in cell lysates. TFPI-Ag was also detected by immunofluorescence staining of cells. Actinomycin D partially whereas cycloheximide completely prevented the serum-induced increased expression of TFPI synthesis by these cells, suggesting control primarily at the translational but some at the transcriptional level as well. The Mr of undegraded TFPI in all cases was ~45 kDa and was of full length. TFPI synthesized locally by fibroblasts, vascular smooth muscle cells and cardiac myocytes could play a significant role in regulating TF-initiated extravascular clotting especially since plasma TFPI that may be available at the injury site lacks a portion of the carboxyl segment and is a less efficient inhibitor.

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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