Effects of Increased Arterial Stiffness on Atherosclerotic Plaque Amounts

Abstract

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.