Endothelial Cells Inhibit Flow-Induced Smooth Muscle Cell Migration

Redmond, Eileen M.; Cullen, John P.; Cahill, Paul A.; Sitzmann, James V.; Stefansson, Steingrimur; Lawrence, Daniel A.; Okada, Satoko

doi:10.1161/01.cir.103.4.597

Cited by 80 publications

(70 citation statements)

References 35 publications

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“…Our results are consistent with observations in diverse systems and with diverse cell types (O'Grady et al 1981;Saksela and Rifkin 1988;Clowes et al 1990;Redmond et al 2001;Jackson and Reidy 1992;Bendeck et al 1994;Stefansson and Lawrence 1996;Werb et al 1997). Migration of human VSMC in vitro has been shown previously to be decreased by PAI-1 (Stefansson and Lawrence 1996;Redmond et al 2001).…”

Section: Figuresupporting

confidence: 92%

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Attenuation of Neointimal Vascular Smooth Muscle Cellularity in Atheroma by Plasminogen Activator Inhibitor Type 1 (PAI-1)

Schneider

Hayes

Wadsworth

et al. 2004

J Histochem Cytochem.

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S U M M A R YRupture of vulnerable atheroma often underlies acute coronary syndromes. Vulnerable plaques exhibit a paucity of vascular smooth muscle cells (VSMCs) in the cap. Therefore, decreased VSMC migration into the neointima may predispose to vulnerability. The balance between cell surface plasminogen activator activity and its inhibition [mediated primarily by plasminogen activator inhibitor type 1 (PAI-1)] modulates migration of diverse types of cells. We sought to determine whether increased expression of PAI-1 would decrease migration of VSMCs in vitro and neointimal cellularity in vivo in apolipoprotein E knockout (ApoE Ϫ / Ϫ ) mice fed a high-fat diet. Increased vessel wall expression of PAI-1 in transgenic mice was induced with the SM22 ␣ promoter. VSMC migration through Matrigel in vitro was quantified with laser scanning cytometry. Expression of PAI-1 was increased threefold in the aortic wall of SM22-PAI transgene-positive mice. Neointimal cellularity of vascular lesions was decreased by 26% ( p ϭ 0.01; n ϭ 5 each) in ApoE Ϫ / Ϫ mice with the SM22-PAI transgene compared with ApoE Ϫ / Ϫ mice. VSMCs explanted from transgenepositive mice exhibited twofold greater expression of PAI-1 and their migration was attenuated by 27% ( p ϭ 0.03). Accordingly, increased expression of PAI-1 protein by VSMCs reduces their migration in vitro and their contribution to neointimal cellularity in vivo. A therogenesis is a multifactorial and prolonged process (Ross 1993). Atherosclerotic plaques particularly prone to rupture, so-called vulnerable plaques, are pivotal in the genesis of acute coronary syndromes (Davies and Thomas 1985;Falk et al. 1995;Libby 1995;Sobel 1999;Sobel et al. 2003). Such plaques have a relative paucity of vascular smooth muscle cells (VSMCs), thin fibrous caps, lipid-laden cores, and high ratios of lipid and extracellular matrix (ECM) to VSMCs. Macrophages and T-lymphocytes, especially in shoulder regions of vulnerable plaques and implicated in plaque rupture (Libby 1995), are relatively prominent cellular constituents, whereas VSMCs are not (Davies and Thomas 1985;Falk et al. 1995;Libby 1995;Sobel 1999;Sobel et al. 2003).We have hypothesized that limitation of activation of intramural plasminogen activators by their primary inhibitor, plasminogen activator inhibitor type 1 (PAI-1), is one factor predisposing to evolution of vulnerable plaques by promoting or retarding neointimal migration of VSMCs, leading to a paucity of such cells and consequent elaboration of thin rather than thick fibrous plaques (Sobel 1999;Sobel et al. 2003). The present study was performed to determine whether decreased migration of VSMCs, characterized in vitro, would ensue if VSMC expression of PAI-1 were increased with the use of the promoter region of the VSMC gene SM-22 ␣ . In addition, we determined whether neointimal cellularity would be diminished in vivo by overexpression of VSMC PAI-1 during the evolution of atheroma in apolipoprotein E (ApoE)-deficient mice. A specific objective was to characterize the effect...

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Section: Figuresupporting

confidence: 92%

“…Migration of human VSMC in vitro has been shown previously to be decreased by PAI-1 (Stefansson and Lawrence 1996;Redmond et al 2001). Administration of a plasmin inhibitor, tranexamic acid, suppressed VSMC migration after injury of rat carotid arteries (Jackson and Reidy 1992).…”

Section: Figurementioning

confidence: 85%

Attenuation of Neointimal Vascular Smooth Muscle Cellularity in Atheroma by Plasminogen Activator Inhibitor Type 1 (PAI-1)

Schneider

Hayes

Wadsworth

et al. 2004

J Histochem Cytochem.

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“…Coculturing of HUVEC in transwells inserted in a 24-well plate with confluent monolayers of SMC is a basic model of vascular wall, which has been demonstrated in other previous studies. 7,9,10,11,21 In the present study, SMC proliferation and migration of SMC to the endothelial cell layer 1 could not be demonstrated in our short time of investigation. The previous study in saphenous vein culture demonstrated TNF-regulated SMC proliferation and migration within 7 days.…”

Section: Discussioncontrasting

confidence: 64%

“…To date, no in vitro vascular model has been demonstrated for pharmacological studies in atherosclerosis, even though there have been several studies with other vascular diseases. [9][10][11] In the present study, we first constructed the in vitro model vascular wall with endothelial cell dysfunction in eNOS production by TNF-to mimic the important basic early stage pathology of atherosclerosis, and determined the potential of the model by using E2 as an antiatheroslerogenic agent. …”

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confidence: 99%

Improvement of Function and Morphology of Tumor Necrosis Factor-.ALPHA. Treated Endothelial Cells With 17-.BETA. Estradiol A Preliminary Study for a Feasible Simple Model for Atherosclerosis

Suwannaprapha

Chaisri

Riyong

et al. 2005

Circ J

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n normal vasculature endothelial cells (EC), a small amount of NO synthesized by endothelial nitric oxide synthase (eNOS) maintains normal vascular physiological function controls. 1,2 Endothelial cell dysfunction in eNOS expression by tumor necrosis factor-(TNF-) is involved in the pathogenesis of vascular diseases, for example atherosclerosis. 3 The related pathologic changes are increased expression of adhesion molecules, including intercellular adhesion molecule (ICAM)-1, vascular adhesion molecule (VCAM)-1, and E-selectin that enhances inflammatory cell infiltration in the vascular wall, platelet aggregation and adhesion on EC surfaces, and smooth muscle cell proliferation and migration. 1,4 In contrast, 17-estradiol (E2) upregulates eNOS production in EC, protects against atherosclerosis and recovers EC after arterial injury in animal models. [5][6][7] At present, experimental models for pathological and pharmacological studies in atherosclerosis have been developed only in laboratory models, eg, primates, rats and mice. 5,6,8 The important defects in the animal models are their complicated metabolisms with systemic variation and the difficulty of controlling the concentrations of drugs acting directly on the target cells. To date, no in vitro vascular model has been demonstrated for pharmacological studies in atherosclerosis, even though there have been several studies with other vascular diseases. [9][10][11] In the present study, we first constructed the in vitro model vascular wall with endothelial cell dysfunction in eNOS production by TNF-to mimic the important basic early stage pathology of atherosclerosis, and determined the potential of the model by using E2 as an antiatheroslerogenic agent. Methods Endothelial Cell CultureHuman umbilical vein endothelial cells (HUVEC) were separated from fresh umbilical cord veins, as previously described. 12 The HUVEC were cultured in human endothelial-SFM basal growth medium (Gibco BRL, Gaithersburg, MD, USA) supplemented with 10% heat-inactivated fetal bovine serum (FBS), 40 g/ml gentamycin and glutamine. The HUVEC were incubated at 37°C in a 5% CO2 atmosphere. Positive staining for CD31 confirmed the endothe- Background Dysfunction of endothelial cells (EC) to produce endothelial nitric oxide synthase (eNOS) by tumor necrosis factor-(TNF-) causes critical features of vascular inflammation associated with several disease states (eg, atherosclerosis including increased platelet aggregation and adhesion on EC, elevated adhesion molecules and enhanced inflammatory cells binding to EC). 17-estradiol (E2) can stimulate eNOS production and improve the critical features of atherosclerosis. Using TNF-and E2, we attempted to develop an in vitro vascular model for studying atherosclerosis. Methods and ResultsHuman umbilical vein endothelial cells (HUVEC) grown in transwells were cocultured with smooth muscle cells in a 24-well plate to mimic the major components of the vascular wall. The model was incubated with TNF-(10 ng/ml) for 12 h, prior exposed to E2 (100 pg/ml) f...

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“…Oscillatory shear stress induces VSMC migration by increasing the expression of MMP-2 and MMP-9 and decreasing plasminogen activator inhibitor-1 (PAI-1) expression [134,135]. In vascular grafts, disturbed flow provides favourable conditions for VSMC proliferation with low shear stress, which may explain, in part, why intimal hyperplasia and atherosclerotic lesions develop preferentially in slow-flow regions [136].…”

mentioning

confidence: 99%

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

Qiu

Zheng

et al. 2014

J. R. Soc. Interface.

149

115

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Vascular smooth muscle cells (VSMCs) have critical functions in vascular diseases. Haemodynamic factors are important regulators of VSMC functions in vascular pathophysiology. VSMCs are physiologically active in the threedimensional matrix and interact with the shear stress sensor of endothelial cells (ECs). The purpose of this review is to illustrate how haemodynamic factors regulate VSMC functions under two-dimensional conditions in vitro or three-dimensional co-culture conditions in vivo. Recent advances show that high shear stress induces VSMC apoptosis through endothelial-released nitric oxide and low shear stress upregulates VSMC proliferation and migration through platelet-derived growth factor released by ECs. This differential regulation emphasizes the need to construct more actual environments for future research on vascular diseases (such as atherosclerosis and hypertension) and cardiovascular tissue engineering.

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Endothelial Cells Inhibit Flow-Induced Smooth Muscle Cell Migration

Abstract: Flow-induced EC PAI-1 inhibits flow-induced SMC migration in vitro. EC PAI-1 expression may be one of the predominant mechanisms responsible for controlling the process of vascular remodeling.

Cited by 80 publications

References 35 publications

Attenuation of Neointimal Vascular Smooth Muscle Cellularity in Atheroma by Plasminogen Activator Inhibitor Type 1 (PAI-1)

Attenuation of Neointimal Vascular Smooth Muscle Cellularity in Atheroma by Plasminogen Activator Inhibitor Type 1 (PAI-1)

Improvement of Function and Morphology of Tumor Necrosis Factor-.ALPHA. Treated Endothelial Cells With 17-.BETA. Estradiol A Preliminary Study for a Feasible Simple Model for Atherosclerosis

Biomechanical regulation of vascular smooth muscle cell functions: from in vitro to in vivo understanding

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