Jeanpierre Emmanuelle, Le Tourneau Thierry, Zawadzki Christophe, Van Belle Eric, Mouquet Frederic, Susen Sophie, Ezekowitz Michael D, Staels Bart, Jude Brigitte, Corseaux Delphine
Inserm, ERI-9, Lille, France.
Cardiovasc Pathol. 2009 May-Jun;18(3):140-7. doi: 10.1016/j.carpath.2008.03.001. Epub 2008 Apr 23.
Fibrates are peroxisome proliferator-activated receptor alpha (PPARalpha) agonists which modulate many aspects of lipoprotein metabolism and inflammation. They have been recently demonstrated to inhibit in vitro expression of tissue factor (TF), the main initiator of blood coagulation, which probably plays a pivotal role in thrombotic complications after plaque rupture. We investigated whether a 4-week fenofibrate treatment might affect the TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture.
After plaque rupture by balloon angioplasty in atheromatous rabbits, animals were randomized in an untreated group or a group receiving fenofibrate. The TF content of arterial wall and the histological modifications were analyzed after 4 weeks.
Fenofibrate decreased in vivo TF expression (-42%, P<.05) and plaque cholesterol content (P<.01) in iliac arteries. Fenofibrate significantly improved the reendothelialization process by 51% (P<.05) and modified cellular distribution in the plaque toward increased stabilization.
These data indicate that the PPARalpha-activator fenofibrate reduces plaque thrombogenicity and accelerates endothelial regrowth which, altogether, might improve plaque stability. These effects may underlie the preventive effects of fibrate therapy in atherosclerosis complications.
贝特类药物是过氧化物酶体增殖物激活受体α（PPARα）激动剂，可调节脂蛋白代谢和炎症的多个方面。最近已证明它们能抑制组织因子（TF）的体外表达，TF是血液凝固的主要启动因子，可能在斑块破裂后的血栓并发症中起关键作用。我们研究了为期4周的非诺贝特治疗是否会影响血管成形术诱导的兔斑块破裂中的TF表达和细胞改变。
在动脉粥样硬化兔中通过球囊血管成形术造成斑块破裂后，将动物随机分为未治疗组或接受非诺贝特治疗的组。4周后分析动脉壁的TF含量和组织学改变。
非诺贝特降低了体内髂动脉中TF的表达（-42%，P<0.05）和斑块胆固醇含量（P<0.01）。非诺贝特使再内皮化过程显著改善了51%（P<0.05），并使斑块中的细胞分布向增加稳定性的方向改变。
这些数据表明，PPARα激活剂非诺贝特可降低斑块的血栓形成性并加速内皮再生，这可能共同改善斑块稳定性。这些作用可能是贝特类药物治疗对动脉粥样硬化并发症预防作用的基础。
