Stoka Kellie V, Maedeker Justine A, Bennett Lisa, Bhayani Siddharth A, Gardner William S, Procknow Jesse D, Cocciolone Austin J, Walji Tezin A, Craft Clarissa S, Wagenseil Jessica E
Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO 63130.
Department of Biomedical Engineering, Saint Louis University, St. Louis, MO 63130.
J Biomech Eng. 2018 May 1;140(5):0510071-05100710. doi: 10.1115/1.4039175.
Increased arterial stiffness is associated with atherosclerosis in humans, but there have been limited animal studies investigating the relationship between these factors. We bred elastin wildtype (Eln+/+) and heterozygous (Eln+/-) mice to apolipoprotein E wildtype (Apoe+/+) and knockout (Apoe-/-) mice and fed them normal diet (ND) or Western diet (WD) for 12 weeks. Eln+/- mice have increased arterial stiffness. Apoe-/- mice develop atherosclerosis on ND that is accelerated by WD. It has been reported that Apoe-/- mice have increased arterial stiffness and that the increased stiffness may play a role in atherosclerotic plaque progression. We found that Eln+/+Apoe-/- arterial stiffness is similar to Eln+/+Apoe+/+ mice at physiologic pressures, suggesting that changes in stiffness do not play a role in atherosclerotic plaque progression in Apoe-/- mice. We found that Eln+/-Apoe-/- mice have increased structural arterial stiffness compared to Eln+/+Apoe-/- mice, but they only have increased amounts of ascending aortic plaque on ND, not WD. The results suggest a change in atherosclerosis progression but not end stage disease in Eln+/-Apoe-/- mice due to increased arterial stiffness. Possible contributing factors include increased blood pressure and changes in circulating levels of interleukin-6 (IL6) and transforming growth factor beta 1 (TGF-β1) that are also associated with Eln+/- genotype.
动脉僵硬度增加与人类动脉粥样硬化相关,但研究这些因素之间关系的动物研究有限。我们将弹性蛋白野生型(Eln+/+)和杂合型(Eln+/-)小鼠与载脂蛋白E野生型(Apoe+/+)和敲除型(Apoe-/-)小鼠进行杂交,并给它们喂食正常饮食(ND)或西式饮食(WD)12周。Eln+/-小鼠的动脉僵硬度增加。Apoe-/-小鼠在正常饮食下会发生动脉粥样硬化,而西式饮食会加速这一过程。据报道,Apoe-/-小鼠的动脉僵硬度增加,且增加的僵硬度可能在动脉粥样硬化斑块进展中起作用。我们发现,在生理压力下,Eln+/+Apoe-/-小鼠的动脉僵硬度与Eln+/+Apoe+/+小鼠相似,这表明僵硬度的变化在Apoe-/-小鼠的动脉粥样硬化斑块进展中不起作用。我们发现,与Eln+/+Apoe-/-小鼠相比,Eln+/-Apoe-/-小鼠的动脉结构僵硬度增加,但它们仅在正常饮食而非西式饮食下升主动脉斑块数量增加。结果表明,由于动脉僵硬度增加,Eln+/-Apoe-/-小鼠的动脉粥样硬化进展发生了变化,但终末期疾病未变。可能的促成因素包括血压升高以及循环中白细胞介素-6(IL6)和转化生长因子β1(TGF-β1)水平的变化,这些也与Eln+/-基因型相关。