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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

Ettore Porreca
1   The Istituto di Patologia Speciale Medica, Italy
,
Concetta Di Febbo
1   The Istituto di Patologia Speciale Medica, Italy
,
Anna Di Sciullo
5   The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
,
Domenico Angelucci
2   The Istituto di Anatomia Patologica, Italy
,
Mimmo Nasuti
5   The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
,
Paola Vitullo
4   The Istituto di Patologia Generate, Università G. D’Annunzio, Chieti, Italy
,
Marcella Reale
3   The Istituto di Immunologia, Italy
,
Pio Conti
3   The Istituto di Immunologia, Italy
,
Franco Cuccurullo
1   The Istituto di Patologia Speciale Medica, Italy
,
Andreina Poggi
5   The istituto di Ricerche Farmacologiche Mario Negri, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy
› Author Affiliations
Further Information

Publication History

Received 13 December 1995

Accepted after revision 10 April 1996

Publication Date:
26 July 2018 (online)

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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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