Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia

Hirotaka Fukami; Jun Morinaga; Hironori Nakagami; Hiroki Hayashi; Yusuke Okadome; Eiji Matsunaga; Tsuyoshi Kadomatsu; Haruki Horiguchi; Michio Sato; Taichi Sugizaki; Takashige Kuwabara; Keishi Miyata; Masashi Mukoyama; Ryuichi Morishita; Yuichi Oike

Cell Reports Medicine (Nov 2021)

Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia

Hirotaka Fukami,
Jun Morinaga,
Hironori Nakagami,
Hiroki Hayashi,
Yusuke Okadome,
Eiji Matsunaga,
Tsuyoshi Kadomatsu,
Haruki Horiguchi,
Michio Sato,
Taichi Sugizaki,
Takashige Kuwabara,
Keishi Miyata,
Masashi Mukoyama,
Ryuichi Morishita,
Yuichi Oike

Affiliations

Hirotaka Fukami: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Jun Morinaga: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Hironori Nakagami: Department of Health Development and Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
Hiroki Hayashi: Department of Health Development and Medicine, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
Yusuke Okadome: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Eiji Matsunaga: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Tsuyoshi Kadomatsu: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Haruki Horiguchi: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Michio Sato: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Taichi Sugizaki: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Takashige Kuwabara: Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Keishi Miyata: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Masashi Mukoyama: Department of Nephrology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan
Ryuichi Morishita: Department of Clinical Gene Therapy, Osaka University Graduate School of Medicine, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan
Yuichi Oike: Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Center for Metabolic Regulation of Healthy Aging (CMHA), Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Department of Aging and Geriatric Medicine, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-0556, Japan; Corresponding author

Journal volume & issue: Vol. 2, no. 11
p. 100446

Abstract

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Summary: Dyslipidemia is a risk factor for cardiovascular disease (CVD), a major cause of death worldwide. Angiopoietin-like protein 3 (ANGPTL3), recognized as a new therapeutic target for dyslipidemia, regulates the metabolism of low-density lipoprotein-cholesterol (LDL-C) and triglycerides. Here, we design 3 epitopes (E1-E3) for use in development of a peptide vaccine targeting ANGPTL3 and estimate effects of each on obesity-associated dyslipidemia in B6.Cg-Lepob/J (ob/ob) mice. Vaccination with the E3 (32EPKSRFAMLD41) peptide significantly reduces circulating levels of triglycerides, LDL-C, and small dense (sd)-LDL-C in ob/ob mice and decreases obese-induced fatty liver. Moreover, E3 vaccination does not induce cytotoxicity in ob/ob mice. Interestingly, the effect of E3 vaccination on dyslipidemia attenuates development of atherosclerosis in B6.KOR/StmSlc-Apoeshl mice fed a high-cholesterol diet, which represent a model of severe familial hypercholesterolemia (FH) caused by ApoE loss of function. Taken together, ANGPTL3 vaccination could be an effective therapeutic strategy against dyslipidemia and associated diseases.

Published in Cell Reports Medicine

ISSN: 2666-3791 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Medicine (General)
Website: https://www.cell.com/cell-reports-medicine

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