Department of Anesthesiology and Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, Baltimore, MD, USA.
Hypertens Res. 2020 Nov;43(11):1175-1181. doi: 10.1038/s41440-020-0467-4. Epub 2020 May 14.
Mice are the most common animal model to investigate human disease and explore physiology. Mice are practical, cost efficient, and easily used for genetic manipulations. Although variability in cardiac structure and function among mouse strains is well noted, the effect of mouse strain on vascular stiffness indices is not known. Here, we compared mouse strain-dependent differences in key vascular stiffness indices among frequently used inbred mouse strains-C57Bl/6J, 129S, and Bl6/129S. In young healthy animals, baseline blood pressure and heart rate were identical in all strains, and independent of gender. However, both active in vivo and passive ex vivo vascular stiffness indices exhibited distinct differences. Specifically, both male and female 129S animals demonstrated the highest tensile stiffness, were least responsive to acetylcholine-induced vasorelaxation, and showed the lowest pulse wave velocity (PWV), an index of in vivo stiffness. C57Bl/6J mice demonstrated the highest PWV, lowest tensile stiffness, and the highest response to acetylcholine-induced vasorelaxation. Interestingly, within each strain, female mice had more compliant aortas. C57Bl/6J mice had thinner vessel walls with fewer layers, whereas 129S mice had the thickest walls with the most layers. Values in the Bl6/129S mixed background mice fell between C57Bl/6J and 129S mice. In conclusion, we show that underlying vascular properties of different inbred wild-type mouse strains are distinct, despite superficial similarities in blood pressure. For each genetic modification, care should be taken to identify proper controls, and conclusions might need to be verified in more than one strain to minimize the risk of false positive studies.
老鼠是研究人类疾病和探索生理学的最常见动物模型。老鼠具有实用性、成本效益高,并且易于进行基因操作。尽管不同品系的老鼠在心脏结构和功能上存在差异,但老鼠品系对血管僵硬指数的影响尚不清楚。在这里,我们比较了常用近交系小鼠品系(C57Bl/6J、129S 和 Bl6/129S)之间关键血管僵硬指数的品系依赖性差异。在年轻健康的动物中,所有品系的基础血压和心率均相同,且不受性别影响。然而,体内和体外被动血管僵硬指数均存在明显差异。具体来说,雄性和雌性 129S 动物的拉伸僵硬度最高,对乙酰胆碱诱导的血管舒张反应最低,脉搏波速度(PWV)最低,这是体内僵硬度的一个指标。C57Bl/6J 小鼠的 PWV 最高,拉伸僵硬度最低,对乙酰胆碱诱导的血管舒张反应最高。有趣的是,在每个品系中,雌性小鼠的主动脉更具顺应性。C57Bl/6J 小鼠的血管壁较薄,层数较少,而 129S 小鼠的血管壁最厚,层数最多。Bl6/129S 混合背景小鼠的值介于 C57Bl/6J 和 129S 小鼠之间。总之,我们表明,尽管血压相似,但不同近交系野生型小鼠的血管固有特性存在差异。对于每种基因修饰,应注意识别合适的对照,并且可能需要在多个品系中验证结论,以最大程度地降低假阳性研究的风险。