Montreal Heart Institute, Université de Montréal, 5000 Belanger St E, Montréal, Québec, Canada.
Can J Cardiol. 2012 Nov-Dec;28(6):678-86. doi: 10.1016/j.cjca.2012.05.003. Epub 2012 Aug 24.
Atherosclerosis and cardiovascular disease are the leading cause of death worldwide. Atherosclerosis is a complex inflammatory disease that results from lipid accumulation and oxidation in the arterial wall combined with an active inflammatory reaction involving transmigration of monocytes and other inflammatory cells from the blood stream into the vessel wall. Many therapeutic approaches have been tested to treat atherosclerosis and prevent its complications, with statins being the most efficient therapy by reducing the levels of atherogenic lipoproteins and preventing major cardiovascular events. However, the risk of atherothrombotic complications still remains high, causing millions of deaths around the world each year. Extensive research has shed light on the cascade of cellular and molecular events that lead from atherosclerotic plaque formation to its rupture and have highlighted promising new therapeutic targets, each being implicated at different stages of the atherosclerotic plaque formation and progression. In this review, we briefly discuss the potential of high-density lipoprotein-based therapies, given the anti-inflammatory properties of high-density lipoprotein. We then present different approaches that tackle inflammation, including inhibition of 5-lipoxygenase, blockade of P-selectin, use of a viral-derived serpin, and interleukin-1β inhibition. All these targets have shown encouraging results in clinical trials and support the idea that targeting inflammation could reduce cardiovascular complications in patients with coronary artery disease.
动脉粥样硬化和心血管疾病是全球范围内主要的死亡原因。动脉粥样硬化是一种复杂的炎症性疾病,源于动脉壁中脂质的积累和氧化,以及涉及单核细胞和其他炎症细胞从血流向血管壁迁移的活跃炎症反应。已经测试了许多治疗方法来治疗动脉粥样硬化并预防其并发症,其中他汀类药物通过降低致动脉粥样硬化脂蛋白的水平和预防主要心血管事件是最有效的治疗方法。然而,动脉血栓并发症的风险仍然很高,每年导致全球数百万人死亡。广泛的研究揭示了导致动脉粥样硬化斑块形成、破裂的细胞和分子事件级联反应,并突出了有前途的新治疗靶点,每个靶点都在动脉粥样硬化斑块形成和进展的不同阶段起作用。在这篇综述中,我们简要讨论了基于高密度脂蛋白的治疗方法的潜力,因为高密度脂蛋白具有抗炎特性。然后,我们介绍了不同的炎症处理方法,包括抑制 5-脂氧合酶、阻断 P 选择素、使用病毒衍生的丝氨酸蛋白酶抑制剂和抑制白细胞介素-1β。所有这些靶点在临床试验中都显示出令人鼓舞的结果,支持了靶向炎症可以降低冠心病患者心血管并发症的想法。