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ORIGINAL RESEARCH article

Front. Cardiovasc. Med.
Sec. Lipids in Cardiovascular Disease
Volume 11 - 2024 | doi: 10.3389/fcvm.2024.1424064
This article is part of the Research Topic Evidence of Atherogenic Lipoproteins: what we gain from in vitro and in vivo research View all articles

Enhanced Atherosclerosis in Apolipoprotein E Knockout Rabbits: Role of ApoB48-Rich Remnant Lipoproteins

Provisionally accepted
Jianglin Fan Jianglin Fan 1*Yajie Chen Yajie Chen 2Manabu Niimi Manabu Niimi 1Huanyu Zhao Huanyu Zhao 3Xiangming Tang Xiangming Tang 1Fumikazu Matsuhisa Fumikazu Matsuhisa 4Huanjin Zhou Huanjin Zhou 1Yan H. Zhao Yan H. Zhao 1Lu Chen Lu Chen 1Shuji Kitajima Shuji Kitajima 4Akira Sato Akira Sato 1
  • 1 University of Yamanashi, Kofu, Japan
  • 2 School of Pharmacy and Food Engineering, Wuyi University, Jiangmen, China
  • 3 China Medical University, Shenyang, Liaoning Province, China
  • 4 Saga University, Saga, Saga, Japan

The final, formatted version of the article will be published soon.

    Introduction: Apolipoprotein E (apoE) acts as a binding molecule for both the low-density lipoprotein receptor and the lipoprotein receptor-related protein and this function is essential for facilitating the hepatocyte uptake of lipoproteins containing apoB. The absence of apoE leads to increased atherogenicity in both humans and mice, although the precise molecular mechanisms remain incompletely understood.Objectives: This study aimed to investigate the susceptibility of apoE knockout (KO) rabbits, in comparison with wild-type (WT) rabbits, to diet-induced hyperlipidemia and atherosclerosis.Methods: ApoE KO rabbits and WT rabbits were fed a diet containing 0.3% cholesterol for 16 weeks. Plasma lipid levels, lipoproteins, and apolipoproteins were analyzed. Atherosclerosis was evaluated at the endpoint of experiments.In addition, we evaluated the oxidizability of those lipoproteins containing apoB to investigate the possible mechanisms of atherosclerosis.Results: Male apoE KO rabbits showed significantly elevated levels of total cholesterol (TC) and triglycerides compared to control rabbits, while female apoE KO rabbits displayed similar high TC levels, albeit with significantly higher triglyceride levels than WT controls. Notably, both male (2.1-fold increase) and female (1.6-fold increase) apoE KO rabbits exhibited a significantly augmented aortic lesion area compared to WT controls.Pathological examination showed that the increased intimal lesions in apoE KO rabbits were featured by heightened infiltration of macrophages (2.7-fold increase) and smooth muscle cells (2.5-fold increase). Furthermore, coronary atherosclerotic lesions were also increased by 1.8-fold in apoE KO rabbits.Lipoprotein analysis revealed that apoB48-rich beta-very-low-density lipoproteins were notably abundant in apoE KO rabbits, suggesting that these remnant lipoproteins of intestinal origin serve as the primary atherogenic lipoproteins. Moreover, apoB48-rich remnant lipoproteins isolated from apoE KO rabbits exhibited heightened susceptibility to copper-induced oxidation.The findings indicate that apoB48-rich remnant lipoproteins, resulting from apoE deficiency, possess greater atherogenic potential than apoB100-rich remnant lipoproteins, regardless of plasma TC levels.

    Keywords: apoB48, apoE, Atherosclerosis, Chylomicrons, Lipoproteins, Rabbits, Remnant

    Received: 27 Apr 2024; Accepted: 02 Jul 2024.

    Copyright: © 2024 Fan, Chen, Niimi, Zhao, Tang, Matsuhisa, Zhou, Zhao, Chen, Kitajima and Sato. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jianglin Fan, University of Yamanashi, Kofu, Japan

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