Consistent responses of the human vascular smooth muscle cell in culture: Implications for restenosis

Munro, Euan; Chan, Pan F.; Patel, M.; Betteridge, L.; Gallagher, Karen; Schächter, Michael; Sever, Peter; Wolfe, John H.

doi:10.1016/0741-5214(94)90149-x

Cited by 19 publications

(25 citation statements)

References 23 publications

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“…Furthermore, this consistency is also seen in cells taken from different vessels in the same patient, including those from stenotic lesions themselves. 35 By contrast, in confirmation of earlier observations, we have demonstrated that there is wide interindividual diversity in responses. 18 These findings support the assumption that differences in cellular response are reproducible and significant.…”

Section: Discussionsupporting

confidence: 53%

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

et al. 1998

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Background-Vascular smooth muscle cell (VMSC) proliferation is an essential component of myointimal hyperplasia, which is implicated in the failure of 30% to 50% of vascular interventions, such as coronary angioplasty and peripheral vein grafting. We have shown that cells derived from stenotic lesions in infrainguinal vein grafts were significantly more resistant than controls to growth inhibition by heparin. Methods and Results-In a prospective study, we correlated antiproliferative responses to heparin in vitro with graft patency after 1 year. Sixty-two patients with infrainguinal vein grafts were entered into a graft surveillance program for Ն1 year. At operation, saphenous vein segments were explanted for VSMC culture. Cell proliferation in response to fetal calf serum was later determined in the presence and absence of heparin. In 35 cell cultures, including 13 from the above-mentioned patients, [ 3 H]heparin binding was also estimated. VSMCs from patients with patent grafts were significantly more sensitive to growth inhibition by heparin than cells from patients with stenoses (median, 54% versus 20.9%, PϽ0.001), and [ 3 H]heparin binding was strongly correlated with inhibition of proliferation (rϭ0.81). Conclusions-Responsiveness to heparin in cultured VSMCs is a strong predictor of outcome for infrainguinal vein grafts, and reduced sensitivity to heparin is correlated with decreased heparin binding. Relative resistance to the antiproliferative action of heparin may be a marker for aberrant regulation of VSMC growth.

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Section: Discussionsupporting

confidence: 53%

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

et al. 1998

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“…It is well known that the in vitro study of SMCs, especially from human origin, is hindered by the fact that their responses vary considerably among donors. 30,31 To circumvent this, we used an immortalized cell line that we have recently developed, designated as HVTs-SM1. This cell line was developed from human vascular SMCs, stably transfected with a nonreplicative retroviral vector containing a temperature-sensitive (tsA58) mutant of the SV40 large T-antigen.…”

Section: Icam-1 Overexpression In Senescent Human Fibroblasts Is Medimentioning

confidence: 99%

p53-Dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions

Gorgoulis

Pratsinis

Zacharatos

et al. 2005

Laboratory Investigation

107

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Most normal somatic cells enter a state called replicative senescence after a certain number of divisions, characterized by irreversible growth arrest. Moreover, they express a pronounced inflammatory phenotype that could contribute to the aging process and the development of age-related pathologies. Among the molecules involved in the inflammatory response that are overexpressed in senescent cells and aged tissues is intercellular adhesion molecule-1 (ICAM-1). Furthermore, ICAM-1 is overexpressed in atherosclerosis, an agerelated, chronic inflammatory disease. We have recently reported that the transcriptional activator p53 can trigger ICAM-1 expression in an nuclear factor-kappa B (NF-jB)-independent manner (Gorgoulis et al, EMBO J. 2003; 22: 1567-1578. As p53 exhibits an increased transcriptional activity in senescent cells, we investigated whether p53 activation is responsible for the senescence-associated ICAM-1 overexpression. To this end, we used two model systems of cellular senescence: (a) human fibroblasts and (b) conditionally immortalized human vascular smooth muscle cells. Here, we present evidence from both cell systems to support a p53-mediated ICAM-1 overexpression in senescent cells that is independent of NF-jB. We also demonstrate in atherosclerotic lesions the presence of cells coexpressing activated p53, ICAM-1, and stained with the senescence-associated b-galactosidase, a biomarker of replicative senescence. Collectively, our data suggest a direct functional link between p53 and ICAM-1 in senescence and age-related disorders.

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“…Although the latter data were obtained in vitro and therefore subject to the potential criticism that it may not reflect the situation in vivo, the studies were performed using standard methodology which have been extensively validated in other systems. 18,19,30,31 This consideration forms the basis for such extrapolation. Theoretically, there are two potential ways by which ECs might affect SMC migration and proliferation: (1) by elaboration of specific factors affecting SMC migration and proliferation, and/or (2) by direct EC-to-SMC contact.…”

Section: Discussionmentioning

confidence: 99%

Endothelial cells lining transjugular intrahepatic portasystemic shunts originate in hepatic sinusoids: Implications for pseudointimal hyperplasia

Sanyal

Mirshahi

1999

Hepatology

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The phenotype of the endothelial cells (ECs) in the pseudointima of transjugular intrahepatic portasystemic shunts (TIPS) and the mechanisms of pseudointima formation after TIPS were unknown. We hypothesized that TIPS were lined by hepatic sinusoidal ECs, which stimulated the migration of smooth muscle cells (SMCs) into the pseudointima and their proliferation. Studies were done with the following specific aims: (1) isolation of ECs from TIPS pseudointima and comparison of their phenotype with human cirrhotic sinusoidal and vascular ECs derived from hepatic and portal veins as well as aorta, and (2) testing of the effects of TIPS ECs on TIPS-derived SMC migration and proliferation. ECs were isolated from eight TIPS retrieved from liver explants by immunomagnetic separation using monodispersed magnetizable polystyrene beads (Dynabeads M-450) coated with Ulex Europeus 1. EC phenotypes were examined by transmission electron microscopy, factor VIII-related antigen, CD31, CD14, and CD34 expression, uptake of acetylated LDL and secretion of type IV collagen. The effects of EC-conditioned media on SMC migration and proliferation were tested in multiwell chemotaxis chambers and by cell counting, respectively. ECs were obtained from TIPS pseudointima with G95% purity. The phenotype of TIPS-derived ECs matched that of cirrhotic sinusoidal endothelium (both expressed CD14) and differed from that of vascular endothelium (CD14 negative, Weibel-Palade positive). Conditioned media from both stenosed (n ‫؍‬ 3) and nonstenosed (n ‫؍‬ 3) TIPS-derived endothelial cells produced a marked (G100%) P F .001 increase in migration as well as (up to 88%) P F .01 proliferation of SMCs from both stenosed (n ‫؍‬ 3) as well as nonstenosed TIPS (n ‫؍‬ 3). These data indicate that TIPS pseudointima are lined by hepatic sinusoidal endothelial cells, which stimulate pseudointima formation by increasing SMC migration and proliferation. (HEPATOLOGY 1999;29:710-718.) Transjugular intrahepatic portasystemic shunts (TIPS) involve creation of an intrahepatic parenchymal tract between the hepatic and portal veins, which is kept patent by deployment of a fenestrated metal stent across it, thereby decompressing the hypertensive portal vein. 1 Despite the short-term clinical success of this procedure, 2 the long-term use of TIPS has been severely limited by the almost universal recurrence of portal hypertension over time. 1,3 The principal cause of such recurrent portal hypertension is the exuberant ingrowth of tissue (pseudointima) from the surrounding liver into the lumen of the stent eventually narrowing the stent and producing TIPS stenosis. 1,4 Several groups have shown that the pseudointima of TIPS is composed of a layer of endothelial cells (ECs) supported by a collagenous matrix. [5][6][7] We have recently documented that the collagenous matrix of TIPS pseudointima is formed by mesenchymal cells, which have a smooth muscle cell (SMC) phenotype.8 It is well known that ECs affect smooth muscle phenotype and function [9][10][11] and that such effects...

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Consistent responses of the human vascular smooth muscle cell in culture: Implications for restenosis

Abstract: VSMC growth characteristics reflect the individual patient and are maintained in cell culture.

Cited by 19 publications

References 23 publications

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

Vein Graft Stenosis and the Heparin Responsiveness of Human Vascular Smooth Muscle Cells

p53-Dependent ICAM-1 overexpression in senescent human cells identified in atherosclerotic lesions

Endothelial cells lining transjugular intrahepatic portasystemic shunts originate in hepatic sinusoids: Implications for pseudointimal hyperplasia

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