Cysteinyl Leukotriene D4 Induced Vascular Smooth Muscle Cell Proliferation: A Possible Role in Myointimal Hyperplasia

Ettore Porreca; Concetta Di Febbo; Anna Di Sciullo; Domenico Angelucci; Mimmo Nasuti; Paola Vitullo; Marcella Reale; Pio Conti; Franco Cuccurullo; Andreina Poggi

doi:10.1055/s-0038-1650530

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 1996; 76(01): 099-104
DOI: 10.1055/s-0038-1650530

Original Article

Schattauer GmbH Stuttgart

Cysteinyl Leukotriene D₄ Induced Vascular Smooth Muscle Cell Proliferation: A Possible Role in Myointimal Hyperplasia

Authors

Ettore Porreca

¹The Istituto di Patologia Speciale Medica, Italy
Concetta Di Febbo

¹The Istituto di Patologia Speciale Medica, Italy
Anna Di Sciullo

⁵The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
Domenico Angelucci

²The Istituto di Anatomia Patologica, Italy
Mimmo Nasuti

⁵The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
Paola Vitullo

⁴The Istituto di Patologia Generate, Università G. D’Annunzio, Chieti, Italy
Marcella Reale

³The Istituto di Immunologia, Italy
Pio Conti

³The Istituto di Immunologia, Italy
Franco Cuccurullo

¹The Istituto di Patologia Speciale Medica, Italy
Andreina Poggi

⁵The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy

Abstract

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Summary

Cysteinyl leukotrienes (i.e. LTC₄, LTD₄), produced by activated leukocytes or by transcellular metabolism may act at different levels on vascular smooth muscle cells (VSMC) during inflammatory processes or atherosclerosis. We studied the effect of LTC₄, LTD₄, and LTE₄ on the in vitro proliferation of rat VSMC, measured by [³H]-thymidine incorporation and cell count. LTD4 had a stronger stimulatory effect on [³H]-thymidine incorporation than LTC₄, whereas LTE₄ was inactive. The effect of LTD4 on [³H]-thymidine incorporation was dose-dependent, with the maximal activity at 10⁻⁶ M. The stimulatory activity of LTD⁴ was inhibited in a dose-dependent manner by MK-571, a specific LTD⁴ receptor antagonist. In addition, MK-571 (1 mg/kg/day) given for at least 1 day after injury in a model of balloon catheter injury of rat carotid artery, provided effective inhibition of myointimal VSMC proliferation, with a 58% reduction of 5-bromo-2’-deoxyuridine (BrdU) uptake in the neointima and 69% reduction of neointimal thickening. Our data support the importance of inflammatory mechanisms in the pathogenesis of atherosclerosis and suggest a possible role for cysteinyl leukotrienes, specifically LTD⁴, in the control of VSMC proliferation.

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References

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