The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels

Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases....

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Autor principal:	Ren Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	ANGPTL3 ANGPTL8 triglyceride HDL-cholesterol metabolism Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/2d1563e599f149a7bc7aebfb2278067e
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spelling	oai:doaj.org-article:2d1563e599f149a7bc7aebfb2278067e2021-11-16T05:46:18ZThe Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels2297-055X10.3389/fcvm.2021.795370https://doaj.org/article/2d1563e599f149a7bc7aebfb2278067e2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcvm.2021.795370/fullhttps://doaj.org/toc/2297-055XElevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.Ren ZhangFrontiers Media S.A.articleANGPTL3ANGPTL8triglycerideHDL-cholesterolmetabolismDiseases of the circulatory (Cardiovascular) systemRC666-701ENFrontiers in Cardiovascular Medicine, Vol 8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	ANGPTL3 ANGPTL8 triglyceride HDL-cholesterol metabolism Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	ANGPTL3 ANGPTL8 triglyceride HDL-cholesterol metabolism Diseases of the circulatory (Cardiovascular) system RC666-701 Ren Zhang The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
description	Elevated triglyceride (TG) and reduced high-density lipoprotein-cholesterol (HDL-C) plasma levels are risk factors for atherosclerosis and cardiovascular disease. Therefore, a drug that simultaneously reduces TG and increases HDL-C plasma levels has the potential to prevent and treat these diseases. Angiopoietin-like 3 (ANGPTL3) regulates plasma TG and HDL-C levels by inhibiting lipoprotein lipase (LPL) and endothelial lipase (EL), respectively. ANGPTL3 inhibition of LPL requires complex formation with ANGPTL8, which is not required for its inhibition of EL. Therefore, the entire pool of plasma ANGPTL3 can be classified as ANGPTL8-associated ANGPTL3 and ANGPTL8-free ANGPTL3, where the former inhibits LPL and the latter inhibits EL. ANGPTL8 antibodies or inhibitors that block its interactions with ANGPTL3 can disrupt or preclude the ANGPTL3-8 complex formation, resulting in fewer ANGPTL3-8 complexes (reduced LPL inhibition), but more free ANGPTL3 (enhanced EL inhibition). Therefore, ANGPTL8 antagonism increases LPL activity while decreasing EL activity, thus leading to reduced plasma TG while simultaneously increasing HDL-C levels. In humans, carriers of ANGPTL8 truncating variants consistently have lower TG but higher HDL-C levels, supporting this hypothesis.
format	article
author	Ren Zhang
author_facet	Ren Zhang
author_sort	Ren Zhang
title	The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
title_short	The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
title_full	The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
title_fullStr	The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
title_full_unstemmed	The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels
title_sort	potential of angptl8 antagonism to simultaneously reduce triglyceride and increase hdl-cholesterol plasma levels
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/2d1563e599f149a7bc7aebfb2278067e
work_keys_str_mv	AT renzhang thepotentialofangptl8antagonismtosimultaneouslyreducetriglycerideandincreasehdlcholesterolplasmalevels AT renzhang potentialofangptl8antagonismtosimultaneouslyreducetriglycerideandincreasehdlcholesterolplasmalevels
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The Potential of ANGPTL8 Antagonism to Simultaneously Reduce Triglyceride and Increase HDL-Cholesterol Plasma Levels

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