Human thrombin receptor-activating peptide-induced proliferation of cultured vascular smooth muscle cells exhibits species specificity

1995 ◽  
Vol 35 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Coleen A. McNamara ◽  
Ian J. Sarembock ◽  
Lawrence W. Gimple ◽  
John W. Fenton ◽  
Gary K. Owens
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Species Specificity ◽  
Thrombin Receptor ◽  
Human Thrombin

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

Surface thrombomodulin modulates thrombin receptor responses on vascular smooth muscle cells

1996 ◽  
Vol 270 (2) ◽  
pp. H603-H609 ◽  
Author(s):  
B. W. Grinnell ◽  
D. T. Berg
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Cell Line ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Cellular Responses ◽  
Thrombin Receptor ◽  
Mitogenic Response ◽  
Agonist Peptide

Vascular smooth muscle cells produce the proteolytically activated thrombin receptor. Under certain conditions, they have been reported to synthesize thrombomodulin (TM), another thrombin receptor known to convert the specificity of thrombin from cleavage of procoagulant/proinflammatory substrates to the cleavage of the anticoagulant/anti-inflammatory factor protein C. In this study, we examined the role of TM in modulating thrombin-mediated cellular responses. Using a thrombin receptor-positive TM-negative rabbit intimal smooth muscle cell line (RIC), we isolated cells expressing varying levels of functional surface TM after transfection with an expression vector containing the cDNA for full-length TM. The parent RIC (TM negative) line responded to alpha-thrombin and to agonist peptide (SFLLRN-PNDKYEPF; abbreviated SFLL) with both mitogenic response and phosphoinositol release. However, transfected cells producing high levels of TM, equivalent to the level on rabbit aortic endothelial cells, responded to SFLL but not to alpha-thrombin. Whereas alpha-thrombin, SFLL, and the combination of SFLL and thrombin resulted in a mitogenic response in the TM-negative RIC line, the response to the agonist peptide could be blocked by thrombin in the TM-producing cell line. The degree to which thrombin receptor activation was blocked directly correlated with the level of TM on the cell surface, and high levels of thrombin could overcome the inhibitory effect. Our data demonstrate that the coexpression of TM with thrombin receptor on vascular smooth muscle cells can result in a modulation of cellular responses to thrombin, which could control thrombin-induced proliferative events following vessel injury or insult.

Thrombin Activates NF-?B through Thrombin Receptor and Results in Proliferation of Vascular Smooth Muscle Cells: Role of Thrombin in Atherosclerosis and Restenosis

1997 ◽  
Vol 811 (1 Atheroscleros) ◽  
pp. 429-436 ◽  
Author(s):  
IKURO MARUYAMA ◽  
KOICHIRO SHIGETA ◽  
HIRONORI MIYAHARA ◽  
TOSHIHIRO NAKAJIMA ◽  
HIROSHI SHIN ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells ◽  
Thrombin Receptor

Thrombin Receptor Activating Peptide (TRAP) Stimulates Mitogenesis, c-fos and PDGF-A Gene Expression in Human Vascular Smooth Muscle Cells

1995 ◽  
Vol 74 (05) ◽  
pp. 1340-1347 ◽  
Author(s):  
Chryso Kanthou ◽  
Omar Benzakour ◽  
Geeta Patel ◽  
John Deadman ◽  
Vijay Vir Kakkar ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Receptor Occupancy ◽  
Muscle Cells ◽  
Signalling Pathways ◽  
Thrombin Receptor ◽  
Computer Assisted ◽  
Computer Assisted Image

SummaryThe synthetic peptide SFLLRNPNDKYEPF, identical in sequence to the new amino-terminus of the thrombin receptor generated following cleavage by thrombin, acts as a thrombin receptor agonist/ activating peptide (TRAP). In this study, Northern blot analysis showed that cultured human vascular smooth muscle cells (HVSMC) express a thrombin receptor transcript. TRAP, in contrast to thrombin was shown to be a weak mitogen for HVSMC. A combination of TRAP and enzymatically-inactivated thrombin (PPACK-thrombin) which provides receptor occupancy, did not potentiate TRAP-induced mitogenesis, indicating that TRAP and PPACK-thrombin do not reproduce the mitogenic effect of enzymatically-active thrombin. Both thrombin and TRAP, induced the expression of c-fos and the PDGF-A gene in a pertussis toxin (PTX)-insensitive manner. Examination of thrombin and TRAP-treated cells by immunofluorescence staining followed by computer assisted image analysis revealed that thrombin and to a lesser extent TRAP induced PDGF-AA protein expression. Antibodies to PDGF-AA partially inhibited thrombin but not TRAP-induced mitogenesis in HVSMC. This study indicates that in addition to the common signalling pathways utilised by thrombin and TRAP, enzymatically-active thrombin activates other signalling pathways and hence TRAP does not mimic fully the biological effect of thrombin on HVSMC.

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