Atherosclerosis Research Unit, Institute of Clinical Medicine and Department of Cardiology, Aarhus University Hospital, Skejby, Aarhus, Denmark.
Curr Opin Lipidol. 2010 Oct;21(5):434-40. doi: 10.1097/MOL.0b013e32833ded6a.
Genetically-engineered mice with hyperlipidemia are the most widely used atherosclerosis models today, but recent advances in transgenesis open the possibility to create new models in alternative species, such as the rat and pig. It seems relevant at this point in time to review some of the strengths and weaknesses of the mouse.
The histology of lesion development in mouse and man has more similarities than differences, and comparative genetics show that many mechanisms of murine and human atherogenesis are shared. Unfortunately, the most feared complication of human atherosclerosis, that is, plaque rupture and thrombosis, occur extremely rarely in mice. This is a major problem. Most patients today are not treated before symptoms ensue, and at this late stage of the disease, mechanisms identified during plaque development in the mouse may not be very important.
Murine atherosclerosis models are highly valuable for identifying atherogenic mechanisms that can be targeted by preventive medicine. However, models with thrombotic complications and large animal models suitable for interventional procedures and imaging would be more supportive for current clinical practice and are highly wanted.
目前,患有高血脂症的基因工程小鼠是最广泛使用的动脉粥样硬化模型,但转基因技术的最新进展为在替代物种(如大鼠和猪)中创建新模型开辟了可能性。此时,回顾一下小鼠的一些优缺点似乎很重要。
小鼠和人类的病变发展组织学具有更多的相似之处,而比较遗传学表明,鼠类和人类动脉粥样硬化形成的许多机制是共有的。不幸的是,人类动脉粥样硬化最可怕的并发症,即斑块破裂和血栓形成,在小鼠中极为罕见。这是一个主要问题。如今,大多数患者在出现症状之前都没有得到治疗,而在疾病的晚期阶段,在小鼠的斑块发展过程中确定的机制可能并不十分重要。
小鼠动脉粥样硬化模型对于鉴定可通过预防医学靶向的动脉粥样硬化机制非常有价值。然而,具有血栓并发症的模型和适合介入性程序和成像的大动物模型将更支持当前的临床实践,这是非常需要的。