The Regulation of p42/p44 Mitogen-Activated Protein Kinases in the Injured Rat Carotid Artery

Lille, Sean; Daum, Günter; Clowes, Monika M.; Clowes, Alexander W.

doi:10.1006/jsre.1997.5114

Cited by 46 publications

(23 citation statements)

References 46 publications

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“…All these events may occur in the vessel wall after plaque rupture. Although previous reports have demonstrated the activation of MAP kinases in arteries in animal models of balloon injury and neointimal formation, [25][26][27][28] our study provides evidence that TF can link activation of blood coagulation and SMC proliferation. In this respect, inhibition of these new functions of TF may represent a novel, attractive therapeutic target.…”

Section: Discussioncontrasting

confidence: 65%

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

et al. 2004

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Background-Tissue factor (TF) is the main initiator of coagulation in vivo. Recently, however, a role for TF as a cell receptor involved in signal transduction has been suggested. The aim of the present study was to assess whether activated factor VII (FVIIa) binding to TF could induce smooth muscle cell (SMC) proliferation and to clarify the possible intracellular mechanism(s) responsible for this proliferation. Methods and Results-Cell proliferation was induced by FVIIa in a dose-dependent manner, as assessed by [3 H]thymidine incorporation and direct cell counting, whereas no response was observed with active site-inhibited FVIIa (FVIIai), which is identical to FVIIa but is devoid of enzymatic activity. Similarly, no proliferation was observed when binding of FVIIa to TF was prevented by the monoclonal anti-TF antibody AP-1. Activation of the p44/42 mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinases 1 and 2 [ERK 1/2]) pathway on binding of FVIIa to TF was demonstrated by transient ERK phosphorylation in Western blots and by suppression of proliferation with the specific MEK (MAP kinase/ERK kinase) inhibitor UO126. ERK phosphorylation was not observed with FVIIai or when cells were pretreated with AP-1. Conclusions-These data indicate a specific effect by which binding of FVIIa to TF on the surface of SMCs induces proliferation via a coagulation-independent mechanism and possibly indicate a new link between coagulation, inflammation, and atherosclerosis. Key Words: coagulants Ⅲ signal transduction Ⅲ cell division T issue factor (TF) is a cell surface-anchored glycoprotein that binds both the zymogen factor VII (FVII) and the active serine protease factor VIIa (FVIIa). 1 TF/FVIIa complex activates coagulation by cleaving its natural substrates, factors IX and X, ultimately leading to thrombin generation, fibrin deposition, and platelet activation. 1,2 On these grounds, TF has been considered to function as a major initiator of blood coagulation in vivo. Recently, however, some evidence has suggested that TF may mediate important coagulationindependent biological phenomena, including embryonic and oncogenic angiogenesis, 3,4 and inflammation. 5 In addition, recent data indicate that TF/FVIIa interaction may activate different intracellular signals, culminating in a variety of cell responses, thus suggesting a role for TF as a "true" cell membrane receptor. For example, TF/FVIIa interaction has been shown to be a strong chemotactic stimulus for smooth muscle cells (SMCs), mediating their migration in vitro. 6 FVIIa has been also shown to induce phosphorylation of the extracellular signalregulated kinases 1 and 2 (ERK 1/2) 7 and to upregulate poly(A) polymerase, 8 urokinase-type plasminogen activator receptor, 9 and a host of genes identified with the use of cDNA microarrays. 10 However, despite evidence suggesting close links between TF, activation of coagulation, and intracellular signaling, no direct effects of TF/FVIIa on SMC proliferation have yet been demonstrated. Thus, in the pr...

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Section: Discussioncontrasting

confidence: 65%

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

et al. 2004

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“…18 Recently it has been shown that MAPK activity is transiently activated following vessel wall injury using a balloon catheter. 19 In this regard, it is possible that certain proteins, such as B1KR, that are differentially expressed following vascular injury may be playing a role in this increased activity of MAPK.…”

Section: Discussionmentioning

confidence: 99%

Induction of B ₁ -Kinin Receptors in Vascular Smooth Muscle Cells: Cellular Mechanisms of MAP Kinase Activation

2001

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Abstract-Vascular smooth muscle cell (VSMC) proliferation is a prominent feature of the atherosclerotic process that occurs after endothelial injury. Although a vascular wall kallikrein-kinin system has been described, its contribution to vascular disease remains undefined. Because the B 1 -kinin receptor subtype (B1KR) is induced in VSMCs only in response to injury, we hypothesize that this receptor may be mediating critical events in the progression of vascular disease. In the present study, we provide evidence that des-Arg 9 -bradykinin (dABK) (10 Ϫ8 M), acting through B1KR, stimulates the phosphorylation of mitogen-activated protein kinase (MAPK) (p42 mapk and p44 mapk ). Activation of MAPK by dABK is mediated via a cholera toxin-sensitive pathway and appears to involve protein kinase C, Src kinase, and MAPK kinase. These findings demonstrate that the activation of B1KR in VSMCs leads to the generation of second messengers that converge to activate MAPK and provide a rationale to investigate the mitogenic actions of dABK in vascular injury.

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“…In vivo, ERK1/2 is transiently activated by acute hypertension 72 and by vessel wall injury with a balloon catheter. 73,74 Diverse pathways link mechanical strain to MAP kinase activation in vascular cells. Hence, G-protein and calciumindependent PKC activation is involved in ERK1/2 activation by shear stress, 70 whereas in certain conditions JNK may be more activated by shear than ERK1/2, through sequential phosphorylation of Sos, Ras, and MEKK.…”

Section: Map Kinase Cascade: Upstream Eventsmentioning

confidence: 99%

Signal Transduction of Mechanical Stresses in the Vascular Wall

1998

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Abstract-The vascular wall is constantly subjected to a variety of mechanical forces in the form of stretch (tensile stress), due to blood pressure, and shear stress, due to blood flow. Alterations in either of these stresses are known to result in vascular remodeling, an adaptation characterized by modified morphology and function of the blood vessels, allowing the vessels to cope with physiological or pathological conditions. The processes involved in vascular remodeling include cellular hypertrophy and hyperplasia, as well as enhanced protein synthesis or extracellular matrix protein reorganization. In vitro studies using vascular cells have attempted to identify the mechanisms behind structural alterations. Possible pathways include ion channels, integrin interaction between cells and the extracellular matrix, activation of various tyrosine kinases (such as c-Src, focal adhesion kinase, and mitogen-activated protein kinases), and autocrine production and release of growth factors. These pathways lie upstream of de novo synthesis of immediate response genes and total protein synthesis, both of which are likely to be involved in the process of vascular remodeling.(Hypertension. 1998;32:338-345.)Key Words: shear stress Ⅲ stretch Ⅲ muscle, smooth Ⅲ endothelium Ⅲ MAP kinases B lood vessels are permanently subjected to mechanical forces in the form of stretch, which because of the pulsatile nature of blood flow exposes vessels to cyclic mechanical strain, and shear stress. Blood pressure is the major determinant of vessel stretch. It creates radial and tangential forces that counteract the effects of intraluminal pressure and that affect all cell types in the vessel. In comparison, fluid shear stress results from the friction of blood against the vessel wall, and it acts in parallel to the vessel surface. Accordingly, shear is sensed principally by endothelial cells, strategically located at the interface between the blood and the vessel wall. Alterations in stretch or shear stress invariably produce transformations in the vessel wall that will aim to accommodate the new conditions and ultimately restore basal levels of tensile stress and shear stress.1-3 Hence, while acute changes in stretch or shear stress correlate with transient adjustments in vessel diameter, mediated through release of vasoactive agonists or change in myogenic tone, chronically altered mechanical forces usually instigate important adaptive alterations of vessel wall shape and composition. The concept of vascular remodeling has therefore been used to describe the transformations that occur in vessels undergoing mechanical stresses. For example, experimental hypertension is accompanied by increased wall thickness, resulting in resistance arteries and arterioles from VSMC hyperplasia and in conductance arteries from hypertrophy. 4,5 Likewise, reduced mechanical strain translates into vessel atrophy.Several reports describe the effects of mechanical stretch on hypertrophy of the heart, and the pathways leading to these events have been studied e...

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The Regulation of p42/p44 Mitogen-Activated Protein Kinases in the Injured Rat Carotid Artery

Cited by 46 publications

References 46 publications

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Induction of B ₁ -Kinin Receptors in Vascular Smooth Muscle Cells: Cellular Mechanisms of MAP Kinase Activation

Signal Transduction of Mechanical Stresses in the Vascular Wall

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The Regulation of p42/p44 Mitogen-Activated Protein Kinases in the Injured Rat Carotid Artery

Cited by 46 publications

References 46 publications

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Tissue Factor Binding of Activated Factor VII Triggers Smooth Muscle Cell Proliferation via Extracellular Signal–Regulated Kinase Activation

Induction of B 1 -Kinin Receptors in Vascular Smooth Muscle Cells: Cellular Mechanisms of MAP Kinase Activation

Signal Transduction of Mechanical Stresses in the Vascular Wall

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Induction of B ₁ -Kinin Receptors in Vascular Smooth Muscle Cells: Cellular Mechanisms of MAP Kinase Activation