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Hypertension and decreased aortic compliance due to reduced elastin amounts do not increase atherosclerotic plaque accumulation in Ldlr−/− mice

      Highlights

      • Elastin insufficient (Eln+/−) mice have hypertension and reduced aortic compliance.
      • Eln+/−Ldlr−/− mice do not have more atherosclerotic plaque than Eln+/+Ldlr−/− mice.
      • Hypertension and reduced aortic compliance may not directly affect atherosclerosis.

      Abstract

      Background and aims

      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.

      Methods and results

      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).

      Conclusion

      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.

      Keywords

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