Feig Jonathan E, Quick John S, Fisher Edward A
New York University School of Medicine, The Marc and Ruti Bell Vascular Biology Disease Program, Department of Cell Biology and Medicine, 550 First Avenue, New York, NY 10016, USA.
Curr Opin Investig Drugs. 2009 Mar;10(3):232-8.
Atherosclerosis is the leading cause of death worldwide. To date, the use of statins to lower LDL levels has been the major intervention used to delay or halt disease progression. These drugs have an incomplete impact on plaque burden and risk, however, as evidenced by the substantial rates of myocardial infarctions that occur in large-scale clinical trials of statins. Thus, it is hoped that by understanding the factors that lead to plaque regression, better approaches to treating atherosclerosis may be developed. A transplantation-based mouse model of atherosclerosis regression has been developed by allowing plaques to form in a model of human atherosclerosis, the apoE-deficient mouse, and then placing these plaques into recipient mice with a normolipidemic plasma environment. Under these conditions, the depletion of foam cells occurs. Interestingly, the disappearance of foam cells was primarily due to migration in a CCR7-dependent manner to regional and systemic lymph nodes after 3 days in the normolipidemic (regression) environment. Further studies using this transplant model demonstrated that liver X receptor and HDL are other factors likely to be involved in plaque regression. In conclusion, through the use of this transplant model, the process of uncovering the pathways regulating atherosclerosis regression has begun, which will ultimately lead to the identification of new therapeutic targets.
动脉粥样硬化是全球主要的死亡原因。迄今为止，使用他汀类药物降低低密度脂蛋白（LDL）水平一直是用于延缓或阻止疾病进展的主要干预措施。然而，这些药物对斑块负担和风险的影响并不完全，他汀类药物大规模临床试验中发生的心肌梗死高发生率就证明了这一点。因此，人们希望通过了解导致斑块消退的因素，开发出更好的治疗动脉粥样硬化的方法。通过在人类动脉粥样硬化模型载脂蛋白E缺乏小鼠中形成斑块，然后将这些斑块移植到具有正常血脂血浆环境的受体小鼠体内，建立了一种基于移植的动脉粥样硬化消退小鼠模型。在这些条件下，泡沫细胞会减少。有趣的是，在正常血脂（消退）环境中3天后，泡沫细胞的消失主要是由于以CCR7依赖的方式迁移至局部和全身淋巴结。使用该移植模型的进一步研究表明，肝X受体和高密度脂蛋白（HDL）是可能参与斑块消退的其他因素。总之，通过使用这种移植模型，揭示调节动脉粥样硬化消退途径的过程已经开始，这最终将导致确定新的治疗靶点。
