Cysteinyl leukotriene D4 induced vascular smooth muscle cell proliferation: a possible role in myointimal hyperplasia
Autor: | Franco Cuccurullo, Ettore Porreca, Domenico Angelucci, Andreina Poggi, Mimmo Nasuti, P Vitullo, A Di Sciullo, Pio Conti, C. Di Febbo, Marcella Reale |
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Rok vydání: | 1996 |
Předmět: |
Neointima
medicine.medical_specialty Vascular smooth muscle Leukotriene D4 Biology Muscle Smooth Vascular chemistry.chemical_compound Internal medicine medicine Animals Cells Cultured Receptors Leukotriene Leukotriene E4 Leukotriene Hyperplasia Leukotriene C4 Balloon catheter Membrane Proteins Hematology respiratory system medicine.disease Rats Endocrinology chemistry Immunology Quinolines Leukotriene Antagonists lipids (amino acids peptides and proteins) Propionates Tunica Intima Cell Division |
Zdroj: | Thrombosis and haemostasis. 76(1) |
ISSN: | 0340-6245 |
Popis: | SummaryCysteinyl 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. |
Databáze: | OpenAIRE |
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