Targeting angiopoietin-like 3 in atherosclerosis: From bench to bedside.
ANGPTL3
atherosclerosis
lipid metabolism
therapy
Journal
Diabetes, obesity & metabolism
ISSN: 1463-1326
Titre abrégé: Diabetes Obes Metab
Pays: England
ID NLM: 100883645
Informations de publication
Date de publication:
09 2021
09 2021
Historique:
revised:
10
05
2021
received:
28
02
2021
accepted:
23
05
2021
pubmed:
29
5
2021
medline:
12
8
2021
entrez:
28
5
2021
Statut:
ppublish
Résumé
Atherosclerotic cardiovascular disease (ASCVD) is the largest cause of morbidity and mortality worldwide. Lipid-lowering therapies are the current major cornerstone of ASCVD management. Statins, ezetimibe, fibrates and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors effectively reduce the plasma low-density lipoprotein cholesterol (LDL-C) level in most individuals at risk of atherosclerosis. Still, some patients (such as those with homozygous familial hypercholesterolaemia), who do not respond to standard therapies, and other patients who cannot take these agents, remain at a high risk of ASCVD. In recent years there has been tremendous progress in understanding the mechanism and efficacy of lipid-lowering strategies. Apart from the recently approved PCSK9 and ATP citrate lyase inhibitors, angiopoietin-like 3 (ANGPTL3) is another potential target for the treatment of dyslipidaemia and its clinical sequalae of atherosclerosis. ANGPTL3 is a pivotal modulator of plasma triglycerides (TG), LDL-C and high-density lipoprotein cholesterol (HDL-C) levels, achieved by inhibiting the activities of lipoprotein lipase and endothelial lipase. Familial combined hypolipidaemia is derived from the Angptl3 loss-of-function mutations, which leads to low levels of LDL-C, HDL-C and TG, and has a 34% decreased risk of ASCVD compared with non-carriers. To date, monoclonal antibodies (evinacumab) and antisense oligonucleotides against ANGPTL3 have been investigated in clinical trials for dyslipidaemia therapy. Herein, we review the biology and function of ANGPTL3, as well as the latest developments of ANGPTL3-targeted therapies. We also summarize evidence from basic research to clinical trials, with the aim of providing novel insights into the biological functions of ANGPTL3 and related targeted therapies.
Substances chimiques
ANGPTL3 protein, human
0
Angiopoietin-Like Protein 3
0
Angiopoietin-like Proteins
0
Angiopoietins
0
PCSK9 protein, human
EC 3.4.21.-
Proprotein Convertase 9
EC 3.4.21.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
2020-2034Subventions
Organisme : China International Medical Foundation
Organisme : Hefei Comprehensive National Science Center
Organisme : Local Innovative and Research Teams Project of Guangdong Pearl River Talents Program
ID : 2017BT01S131
Organisme : National Natural Science Foundation of China
ID : 81530025
Organisme : National Natural Science Foundation of China
ID : 81941022
Organisme : National Natural Science Foundation of China
ID : 82070464
Organisme : Natural Science Foundation of Anhui Province
ID : 006223066002
Organisme : Program for Innovative Research Team of The First Affiliated Hospital of USTC
ID : CXGG02
Organisme : Strategic Priority Research Program of Chinese Academy of Sciences
ID : XDB38010100
Organisme : The National Key R&D Program of China
ID : 2017YFC1309603
Informations de copyright
© 2021 John Wiley & Sons Ltd.
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