Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II–Induced Mice

Hiroki Tanaka, Yasunori Iida, Takayuki Iwaki, Yuko Suzuki, Hideto Sano, Chiharu Miyajima, Nobuhiro Zaima, Takeshi Sasaki, Ayato Sumioka, Shogo Hakamata, Hideyuki Shimizu, Kazuo Umemura, Tetsumei Urano

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Background: Plasma low-density lipoprotein (LDL) cholesterol is implicated in abdominal aorta (AA) and aortic dissection (AD); however, its role in the pathogenesis of AA and AD, a disease with a high mortality rate, is unknown. The existing animal models such as apolipoprotein E-deficient (Apoe−/−) mice cannot reproduce all the conditions of AA/AD, including elevated LDL-cholesterol levels and spontaneous atheroma formation; therefore, a more reliable in vivo model is required. Here, we analyzed angiotensin II (Ang II)–induced mice with combined deficiency of the LDL receptor and the catalytic component of the apolipoprotein B-edisome complex (Ldlr−/−/Apobec1−/− [WKO]) to understand AA formation and AD occurrence in relation to plasma lipid composition. Methods: AAs and ADs were created in 18- to 22- week-old male Apoe−/− and Ldlr−/−/Apobec1−/− mice by Ang II infusion. Immunostaining allowed assessment of smooth muscle cells and mural monocytes/macrophages. Results: Ldlr−/−/Apobec1−/− mice had elevated LDL-cholesterol levels characteristic for human type IIa hyperlipidemia, resulting in atherogenesis, which promoted mortality, AA formation, and AD development. Interestingly, variations in the distribution of atheromas and inflammatory sites between Apoe−/− and Ldlr−/−/Apobec1−/− mice depending on lipid profiles resulted in differences in AA formation and AD occurrence in the thoracic aorta. Conclusions: Our results indicate the presence of a pathogenic pathway involving serum lipid composition that plays a key role in AA formation and AD occurrence in Ang II–induced mice.

元の言語English
ページ(範囲)204-213
ページ数10
ジャーナルAnnals of Vascular Surgery
48
DOI
出版物ステータスPublished - 2018 4

ASJC Scopus subject areas

  • Surgery
  • Cardiology and Cardiovascular Medicine

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    Tanaka, H., Iida, Y., Iwaki, T., Suzuki, Y., Sano, H., Miyajima, C., Zaima, N., Sasaki, T., Sumioka, A., Hakamata, S., Shimizu, H., Umemura, K., & Urano, T. (2018). Elevated Plasma Levels of LDL Cholesterol Promote Dissecting Thoracic Aortic Aneurysms in Angiotensin II–Induced Mice. Annals of Vascular Surgery, 48, 204-213. https://doi.org/10.1016/j.avsg.2017.10.006