Maedeker Justine A, Stoka Kellie V, Bhayani Siddharth A, Gardner William S, Bennett Lisa, Procknow Jesse D, Staiculescu Marius C, Walji Tezin A, Craft Clarissa S, Wagenseil Jessica E
Department of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO, USA.
Department of Biomedical Engineering, Saint Louis University, St. Louis, MO, USA.
Atherosclerosis. 2016 Jun;249:22-9. doi: 10.1016/j.atherosclerosis.2016.03.022. Epub 2016 Mar 21.
High blood pressure and reduced aortic compliance are associated with increased atherosclerotic plaque accumulation in humans. Animal studies support these associations, but additional factors, such as fragmented elastic fibers, are present in most previous animal studies. Elastin heterozygous (Eln+/-) mice have high blood pressure and reduced aortic compliance, with no evidence of elastic fiber fragmentation and represent an appropriate model to directly investigate the effects of these factors on atherosclerosis.
Eln+/- and Eln+/+ mice were crossed with low density lipoprotein receptor knockout (Ldlr-/-) and wild-type (Ldlr+/+) mice and fed normal or Western diet (WD) for 16 weeks. We hypothesized that on WD, Eln+/-Ldlr-/- mice with high blood pressure and reduced aortic compliance would have increased atherosclerotic plaque accumulation compared to Eln+/+Ldlr-/- mice. We measured serum cholesterol and cytokine levels, blood pressure, aortic compliance, and plaque accumulation. Contrary to our hypothesis, we found that on WD, Eln+/-Ldlr-/- mice do not have increased plaque accumulation compared to Eln+/+Ldlr-/- mice. At the aortic root, there are no significant differences in plaque area between Eln+/-Ldlr-/- and Eln+/+Ldlr-/- mice on WD (p = 0.89), while in the ascending aorta, Eln+/-Ldlr-/- mice on WD have 29% less normalized plaque area than Eln+/+Ldlr-/- mice on WD (p = 0.009).
Using an atherogenic mouse model, we conclude that increased blood pressure and reduced aortic compliance are not direct causes of increased aortic plaque accumulation. We propose that additional insults, such as fragmentation of elastic fibers, are necessary to alter plaque accumulation.
高血压和主动脉顺应性降低与人类动脉粥样硬化斑块积累增加有关。动物研究支持这些关联，但在大多数先前的动物研究中还存在其他因素，如弹性纤维断裂。弹性蛋白杂合子（Eln+/-）小鼠患有高血压且主动脉顺应性降低，没有弹性纤维断裂的证据，是直接研究这些因素对动脉粥样硬化影响的合适模型。
将Eln+/-和Eln+/+小鼠与低密度脂蛋白受体敲除（Ldlr-/-）和野生型（Ldlr+/+）小鼠杂交，并给予正常或西式饮食（WD）16周。我们假设，在WD饮食条件下，与Eln+/+Ldlr-/-小鼠相比，患有高血压且主动脉顺应性降低的Eln+/-Ldlr-/-小鼠动脉粥样硬化斑块积累会增加。我们测量了血清胆固醇和细胞因子水平、血压、主动脉顺应性和斑块积累情况。与我们的假设相反，我们发现，在WD饮食条件下，与Eln+/+Ldlr-/-小鼠相比，Eln+/-Ldlr-/-小鼠的斑块积累并未增加。在主动脉根部，WD饮食条件下的Eln+/-Ldlr-/-和Eln+/+Ldlr-/-小鼠之间的斑块面积没有显著差异（p = 0.89），而在升主动脉中，WD饮食条件下的Eln+/-Ldlr-/-小鼠的标准化斑块面积比WD饮食条件下的Eln+/+Ldlr-/-小鼠少29%（p = 0.009）。
使用动脉粥样硬化小鼠模型，我们得出结论，血压升高和主动脉顺应性降低不是主动脉斑块积累增加的直接原因。我们提出，诸如弹性纤维断裂等额外损伤对于改变斑块积累是必要的。
