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Growth inhibition of human vascular smooth muscle cells by fenofibrate: A possible therapy for restenosis

Munro, E., Patel, M., Chan, P., Betteridge, L., Gallagher, K., Schachter, M., Wolfe, J., Sever, P. (1994) Growth inhibition of human vascular smooth muscle cells by fenofibrate: A possible therapy for restenosis. Cardiovascular Research, 28 (5). pp. 615-620. ISSN 0008-6363. (doi:10.1093/cvr/28.5.615) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

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Official URL
https://doi.org/10.1093/cvr/28.5.615

Abstract

Objective: The aim was to assess the growth inhibitory effect of fibrates on human vascular smooth muscle cells. Restenosis is the most important factor limiting the long term success of invasive vascular interventions and there is as yet no effective preventive treatment. Platelet derived growth factor (PDGF) is considered to be an important growth promoting agent for vascular smooth muscle cells (VSMC) and fenofibric acid (a hypolipidaemic drug) has been reported to be a PDGF antagonist. Methods: The effect of the fibrate drugs fenofibrate, clofibrate, bezafibrate, and gemfibrozil were examined on the proliferation of cultured human vascular smooth muscle cells derived from saphenous vein (n = 20) and graft stenoses (n = 7). Results: Fenofibrate (100 μM) produced potent inhibition (48%) of VSMC proliferation at a concentration equivalent to that of its circulating metabolite fenofibric acid, but none of the other drugs produced any significant effect on growth. VSMC derived from graft stenoses were equally sensitive to inhibition as saphenous vein derived controls, in contrast to our previous work which reported that graft stenosis derived VSMC were resistant to growth inhibition by the physiological inhibitor heparin. The antiproliferative effect of fenofibrate was independent of inhibition of cellular cholesterol synthesis or toxicity. Fenofibrate inhibited VSMC growth induced by 15% fetal calf serum, PDGF, and basic fibroblast growth factor to a similar degree, indicating that it is not a specific PDGF antagonist. Conclusions: Fenofibrate is not a specific PDGF antagonist. Fenofibric acid, one of the principal metabolites of fenofibrate, did not produce any inhibition of growth, suggesting that oral administration of fenofibrate would not be efficacious. Fenofibrate is the first potent inhibitor to be described for VSMC derived from human myo-intimal hyperplastic lesions.

Item Type: Article
DOI/Identification number: 10.1093/cvr/28.5.615
Uncontrolled keywords: Cell proliferation, Fenofibrate, Human vascular smooth muscle, Restenosis; myointimal hyperplasia, bezafibrate, clofibrate, fenofibrate, gemfibrozil, article, clinical article, clinical trial, controlled clinical trial, controlled study, coronary artery obstruction, growth inhibition, human, human tissue, morphology, priority journal, saphenous vein, vascular smooth muscle, Bezafibrate, Cell Division, Cells, Cultured, Clofibrate, Gemfibrozil, Graft Occlusion, Vascular, Humans, Muscle, Smooth, Platelet-Derived Growth Factor, Procetofen, Saphenous Vein
Divisions: Faculties > Sciences > Kent and Medway Medical School
Depositing User: Philip Chan
Date Deposited: 07 Nov 2019 16:37 UTC
Last Modified: 30 Jan 2020 10:26 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/78353 (The current URI for this page, for reference purposes)
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