Tissue factor pathway inhibitor-2 is induced by fluid shear stress in vascular smooth muscle cells and affects cell proliferation and survival

Ekstrand, Johan; Razuvaev, Anton; Folkersen, Lasse; Roy, Joy; Hedin, Ulf

doi:10.1016/j.jvs.2010.02.282

Cited by 38 publications

(22 citation statements)

References 40 publications

(33 reference statements)

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“…By contrast, TF inhibition via TFPI also caused FAS ligandmediated apoptotic cell death in macrophages (42). In vascular smooth muscle cells, TFPI induction caused inhibition of proliferation and enhanced apoptosis (43). Although TF-mediated fibrin deposition and consequent pathogenesis of airway disease has been reported, we now establish a role of TF in promoting airway epithelial cell and basal cell survival.…”

Section: Discussionmentioning

confidence: 62%

Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and Protease-Activated Receptor Isoforms 1 and 2

Ahmad

Ahmad²,

Rancourt³

et al. 2013

Am J Respir Cell Mol Biol

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Tissue factor (TF) initiates the extrinsic coagulation cascade and is a high-affinity receptor for coagulation factor VII. TF also participates in protease-activated receptor (PAR)1 and PAR2 activation. Human epithelial basal cells were previously purified on the basis of TF expression. The purpose of this study was to determine if tracheobronchial epithelial basal cell-associated TF drives coagulation and/ or activates PARs to promote basal cell functions. We used human tracheobronchial tissues to isolate human airway epithelial cells using specific cell surface markers by flow cytometry and studied TF expression by immunostaining. TF-dependent fibrin network formation was observed by confocal and scanning electron microscopy. TF knockdown was done using short hairpin RNA, and TF mRNA was measured using quantitative RT-PCR. We found that 97 6 5% of firstpassage human tracheobronchial epithelial cells were basal cells, and 100% of these basal cells expressed TF. Basal cell-associated TF was active, but TF activity was dependent on added extrinsic coagulation cascade factors. TF inhibition caused basal cell apoptosis and necrosis. This was due to two parallel but interdependent TFregulated processes: failure to generate a basal cell-associated fibrin network and suboptimal PAR1 and PAR2 activity. The data indicate that membrane surface TF mediates airway epithelial basal cell attachment, which maintains cell survival and mitotic potential. The implications of these findings are discussed in the context of basal cell-associated TF activity in normal and injured tissues and of the potential for repair of airway epithelium in lung disease.Keywords: tissue factor; epithelium; clotting; fibrin; tracheobronchial Tissue factor (TF) is a transmembrane cell receptor and cofactor for factor VII (FVII) and serves biological functions beyond its established role in blood coagulation (1). TF may act as a transmembrane signaling molecule by activating and delivering coagulation factors for signaling, and the TF-coagulation FVIIa complex activates G protein-coupled receptors, including the protease-activated receptors (PARs) (2). Under pathologic conditions, TF can be expressed by circulating blood elements (monocytes, neutrophils, and platelets) and by an associated elevated number of cell-derived circulating microparticles. The role of TF in epithelial cell function is much less well understood than its role in the circulation and in hemostasis.In acute lung injury, increased coagulation and decreased fibrinolysis result in diffuse alveolar fibrin deposition, potentially increasing lung inflammation (3). Recent evidence indicates that the damaged alveolar epithelium expresses TF (4) and that FVII-activating protein expression is increased (5). Alveolar procoagulant microparticles are also elevated (6), and intrinsic elevation of tissue factor pathway inhibitor (TFPI) expression is insufficient to inhibit this procoagulant effect (7). Coagulation pathologies also occur in conducting airways. For example, the sulfur mustard ana...

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Section: Discussionmentioning

confidence: 62%

Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and Protease-Activated Receptor Isoforms 1 and 2

Ahmad

Ahmad²,

Rancourt³

et al. 2013

Am J Respir Cell Mol Biol

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“…In order to identify proliferating cells, the slides were stained using an antibody against proliferating cell nuclear antigen (PCNA; 1:400; DAKO, Glostrup, Denmark) [23]. Three representative areas, evenly spaced, on each vessel were blindly counted to evaluate the percentage of PCNA-positive cells, using ImageJ software [22].…”

Section: Methodsmentioning

confidence: 99%

Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury

Eriksson

Saxelin²,

Röhl³

et al. 2015

J Vasc Res

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Diabetic patients have an increased risk of restenosis and late stent thrombosis after angioplasty, i.e. complications that are related to a defective re-endothelialization. Exendin-4, a stable glucagon-like peptide (GLP)-1 receptor agonist, has been suggested to influence the formation of intimal hyperplasia and to increase endothelial cell proliferation in vitro. Thus, the aim of this study was to investigate the mechanisms by which treatment with exendin-4 could influence re-endothelialization and intimal hyperplasia after vascular injury. Methods: Sprague-Dawley rats were subjected to balloon injury of the left common carotid artery and treated for 4 weeks with exendin-4 or vehicle. Intimal hyperplasia and vessel wall elasticity were monitored noninvasively by high-frequency ultrasound, and re-endothelialization was evaluated upon sacrifice using Evans blue dye. Results and Conclusion: Exendin-4 selectively reduced the proliferation of smooth muscle cells (SMCs) and intimal hyperplasia in vivo without affecting the re-endothelialization process, but treatment with exendin-4 improved arterial wall elasticity. Our data also show that exendin-4 significantly decreased the proliferation and increased the apoptosis of SMCs in vitro, effects that appear to be mediated through cAMP signaling and endothelial nitric oxide synthase following GLP-1 receptor activation. Together, these effects of exendin-4 are highly desirable and may lead to an improved outcome for patients undergoing vascular interventions.

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“…35 Different types of fluid shear stress can evoke a variety of reactions in these cells, including perpetuating the process of fibrous cap instability. 36 Focusing on human carotid artery SMCs (HCtASMCs), considered essential for stabilization of the fibrous cap, 1 we used an isolated system that subjected them to physiological (laminar) or pathological (oscillatory) fluidic flow (Online Figure VIA). When HCtASMCs and human carotid artery endothelial cells were exposed to shear stress of 12 dyn/cm 2 for 24 hours, oscillatory shear stress caused a loss of miR-210 expression in HCtASMCs, but not in endothelial cells ( Figure 5A).…”

Section: Mir-210 Prevents Smc Apoptosis Through Targeting Of Apc In Vmentioning

confidence: 99%

MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

Eken

Jin

Chernogubova

et al. 2017

Circulation Research

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110

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Stroke is the second most common cause of death 2 and major cause of disability worldwide, 2 with survivors often depending on lifelong care. Carotid stenosis is the second most common predecessor of ischemic stroke, 3 and carotid endarterectomy (CEA; and to a lesser extent carotid artery stenting) are accepted as secondary, but also primary preventive therapy. 2,4,5 With new imaging techniques, vulnerable plaques at risk of rupture can be identified with increasing accuracy, 6 but in the majority of cases, the perioperative surgical risk of ≈3% still outweighs the risk of plaque rupture in asymptomatic carotid stenosis carriers.7 As a result, CEA and carotid artery stenting are currently unfavorable for most of these individuals.8 Detection and stabilization of a vulnerable plaque by influencing the local disease process biologically would provide a sophisticated solution for asymptomatic plaque carriers at risk of stroke. Molecular Medicine© 2016 American Heart Association, Inc. Conclusions: An unstable carotid plaque at risk of stroke is characterized by low expression of miR-210. miR-210 contributes to stabilizing carotid plaques through inhibition of APC, ensuring smooth muscle cell survival. We present local delivery of miR-210 as a therapeutic approach for prevention of atherothrombotic vascular events.

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Tissue factor pathway inhibitor-2 is induced by fluid shear stress in vascular smooth muscle cells and affects cell proliferation and survival

Cited by 38 publications

References 40 publications

Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and Protease-Activated Receptor Isoforms 1 and 2

Tissue Factor Signals Airway Epithelial Basal Cell Survival via Coagulation and Protease-Activated Receptor Isoforms 1 and 2

Glucagon-Like Peptide-1 Receptor Activation Does Not Affect Re-Endothelialization but Reduces Intimal Hyperplasia via Direct Effects on Smooth Muscle Cells in a Nondiabetic Model of Arterial Injury

MicroRNA-210 Enhances Fibrous Cap Stability in Advanced Atherosclerotic Lesions

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