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

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,...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	ANGPTL3 peptide vaccine dyslipidemia atherosclerosis fatty liver triglyceride Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e98668609cb34bd8a3fd098985594146
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spelling	oai:doaj.org-article:e98668609cb34bd8a3fd0989855941462021-11-18T04:52:14ZVaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia2666-379110.1016/j.xcrm.2021.100446https://doaj.org/article/e98668609cb34bd8a3fd0989855941462021-11-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2666379121003141https://doaj.org/toc/2666-3791Summary: 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.Hirotaka FukamiJun MorinagaHironori NakagamiHiroki HayashiYusuke OkadomeEiji MatsunagaTsuyoshi KadomatsuHaruki HoriguchiMichio SatoTaichi SugizakiTakashige KuwabaraKeishi MiyataMasashi MukoyamaRyuichi MorishitaYuichi OikeElsevierarticleANGPTL3peptide vaccinedyslipidemiaatherosclerosisfatty livertriglycerideMedicine (General)R5-920ENCell Reports Medicine, Vol 2, Iss 11, Pp 100446- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ANGPTL3 peptide vaccine dyslipidemia atherosclerosis fatty liver triglyceride Medicine (General) R5-920
spellingShingle	ANGPTL3 peptide vaccine dyslipidemia atherosclerosis fatty liver triglyceride Medicine (General) R5-920 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 Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
description	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.
format	article
author	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
author_facet	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
author_sort	Hirotaka Fukami
title	Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
title_short	Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
title_full	Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
title_fullStr	Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
title_full_unstemmed	Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
title_sort	vaccine targeting angptl3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/e98668609cb34bd8a3fd098985594146
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Vaccine targeting ANGPTL3 ameliorates dyslipidemia and associated diseases in mouse models of obese dyslipidemia and familial hypercholesterolemia

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