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.

Cardiovascular protection in females linked to estrogen-dependent inhibition of arterial stiffening and macrophage MMP12

“…In addition to our work, which reveals a likely atheroprotective benefit of reduced arterial stiffness (this report and ref. 10), we note complementary findings by others demonstrating a direct relationship between increased arterial stiffness and increased atherosclerosis in atheroprone mice (49)(50)(51)(52). Two recent reports using heterozygous expression of elastin indicate that increased arterial stiffness likely accelerates (rather than increases the maximal amount of) lesion burden and that this effect may be site specific and involve nonmechanical factors such as blood pressure and circulating soluble factors (49,53).…”

Establishing the interchangeability of arterial stiffness but not endothelial function parameters in healthy individuals

“…In this way, arterial stiffness could replace the less accurate assessment of traditional CVD risk factors that are based on epidemiological studies and are not robust at the individual level. Furthermore, recent evidence suggests that arterial stiffness represents changes associated with atherosclerotic disease progression and is not a factor in end stage disease [46]. Thus, non-invasive determination of arterial function could be a new paradigm for detecting existing early stage asymptomatic atherosclerotic disease in individuals using techniques that are amenable to the clinic setting.…”

Multimodality carotid plaque tissue characterization and classification in the artificial intelligence paradigm: a narrative review for stroke application

“…Plaque formation initially begins with the deposition of small lipid and fatty materials in the intima, which can grow into complex plaque structures over time (65). The advanced plaque has a heterogeneous composition, with a lipid center, calcification, and fibrous deposits of the connective tissue (66).…”