Gisterå Anton, Ketelhuth Daniel F J, Malin Stephen G, Hansson Göran K
Cardiovascular Medicine, Department of Medicine Solna, Karolinska Institutet and Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden (A.G., D.F.J.K., S.G.M., G.K.H.).
Department of Cardiovascular and Renal Research, Institute for Molecular Medicine, University of Southern Denmark (SDU), Odense, Denmark (D.F.J.K).
Circ Res. 2022 Jun 10;130(12):1869-1887. doi: 10.1161/CIRCRESAHA.122.320263. Epub 2022 Jun 9.
Atherosclerotic cardiovascular disease is a major cause of death among humans. Animal models have shown that cholesterol and inflammation are causatively involved in the disease process. Apolipoprotein B-containing lipoproteins elicit immune reactions and instigate inflammation in the vessel wall. Still, a treatment that is specific to vascular inflammation is lacking, which motivates continued in vivo investigations of the immune-vascular interactions that drive the disease. In this review, we distill old notions with emerging concepts into a contemporary understanding of vascular disease models. Pros and cons of different models are listed and the complex integrative interplay between cholesterol homeostasis, immune activation, and adaptations of the vascular system is discussed. Key limitations with atherosclerosis models are highlighted, and we suggest improvements that could accelerate progress in the field. However, excessively rigid experimental guidelines or limiting usage to certain animal models can be counterproductive. Continued work in improved models, as well as the development of new models, should be of great value in research and could aid the development of cardiovascular disease diagnostics and therapeutics of the future.
动脉粥样硬化性心血管疾病是人类死亡的主要原因。动物模型表明,胆固醇和炎症在疾病过程中起着因果作用。含载脂蛋白B的脂蛋白引发免疫反应并在血管壁中引发炎症。然而,目前仍缺乏针对血管炎症的特异性治疗方法,这促使人们继续对驱动该疾病的免疫-血管相互作用进行体内研究。在这篇综述中,我们将旧观念与新观念相结合,形成对血管疾病模型的当代理解。列出了不同模型的优缺点,并讨论了胆固醇稳态、免疫激活和血管系统适应性之间复杂的综合相互作用。强调了动脉粥样硬化模型的主要局限性,并提出了可以加速该领域进展的改进建议。然而,过于严格的实验指南或将使用限制在某些动物模型上可能会适得其反。在改进模型方面的持续工作以及新模型的开发,在研究中应具有重要价值,并有助于未来心血管疾病诊断和治疗的发展。