Porreca E, Di Febbo C, Di Sciullo A, Angelucci D, Nasuti M, Vitullo P, Reale M, Conti P, Cuccurullo F, Poggi A
Istituto di Patologia Speciale Medica, Università G.D'Annuzio, Chieti, Italy.
Thromb Haemost. 1996 Jul;76(1):99-104.
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 process 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.
半胱氨酰白三烯（即LTC4、LTD4）由活化的白细胞产生或通过转细胞代谢产生，在炎症过程或动脉粥样硬化期间可能在不同水平作用于血管平滑肌细胞（VSMC）。我们通过[3H] - 胸腺嘧啶核苷掺入和细胞计数研究了LTC4、LTD4和LTE4对大鼠VSMC体外增殖的影响。LTD4对[3H] - 胸腺嘧啶核苷掺入的刺激作用比LTC4更强，而LTE4无活性。LTD4对[3H] - 胸腺嘧啶核苷掺入的作用呈剂量依赖性，在10(-6) M时活性最大。LTD4的刺激活性被特异性LTD4受体拮抗剂MK - 571以剂量依赖性方式抑制。此外，在大鼠颈动脉球囊导管损伤模型中，损伤后至少1天给予MK - 571（1 mg/kg/天），可有效抑制肌内膜VSMC增殖，新生内膜中5 - 溴 - 2'-脱氧尿苷（BrdU）摄取减少58%，新生内膜增厚减少69%。我们的数据支持炎症机制在动脉粥样硬化发病机制中的重要性，并提示半胱氨酰白三烯，特别是LTD4，在控制VSMC增殖中可能发挥作用。
