Hyperlipidemia does not affect development of elastase-induced abdominal aortic aneurysm in mice

Joscha Mulorz*, Joshua Michael Spin, Hans Christian Beck, My Linh Tha Thi, Markus Udo Wagenhäuser, Lars Melholt Rasmussen, Jes Sanddal Lindholt, Philip Shih Chung Tsao, Lasse Bach Steffensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Background and aims: Hyperlipidemia is a suggested risk factor for abdominal aortic aneurysm (AAA). However, whether hyperlipidemia is causally involved in AAA progression remains elusive. Here, we tested the hypothesis that hyperlipidemia aggravates AAA formation in the widely used porcine pancreatic elastase (PPE) model of AAA in mice with varying levels of plasma lipids. Methods: Prior to PPE-surgery, 8-week-old male C57BL/6J mice (n = 32) received 1·1011 viral genomes of rAAV8-D377Y-mPcsk9 or control rAAV8 via the tail vein. Mice were fed either western type diet or regular chow. At baseline and during the 28 days following PPE-surgery, mice underwent weekly ultrasonic assessment of AAA progression. Experiments were repeated using Apolipoprotein E knockout (ApoE−/−) mice (n = 7) and wildtype C57BL/6J mice (n = 5). Results: At sacrifice, maximal intergroup plasma cholesterol and non-HDL/HDL ratio differences were >5-fold and >20-fold, respectively. AAA diameters expanded to 150% of baseline, but no intergroup differences were detected. This was verified in an independent experiment comparing 8-week-old male ApoE−/− mice with wildtype mice. Histological evaluation of experimental AAA lesions revealed accumulated lipid in neointimal and medial layers, and analysis of human AAA lesions (n = 5) obtained from open repair showed medial lipid deposition. Conclusions: In summary, we find that lipid deposition in the aortic wall is a feature of PPE-induced AAA in mice as well as human AAA lesions. Despite, our data do not support the hypothesis that hyperlipidemia contributes to AAA progression.

Original languageEnglish
JournalAtherosclerosis
Volume311
Pages (from-to)73-83
Number of pages11
ISSN0021-9150
DOIs
Publication statusPublished - Oct 2020

Keywords

  • Abdominal aortic aneurysm
  • Animal model
  • Hyperlipidemia
  • Pathobiology

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