Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function (LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia (FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.

Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia / Tarugi, P.; Bertolini, S.; Calandra, S.. - In: JOURNAL OF BIOMEDICAL RESEARCH. - ISSN 1674-8301. - 33:2(2019), pp. 73-81. [10.7555/JBR.32.20170114]

Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia

Tarugi P.
;
Calandra S.
2019

Abstract

Three members of the angiopoietin-like (ANGPTL) protein family-ANGPTL3, ANGPTL4 and ANGPTL8- are important regulators of plasma lipoproteins. They inhibit the enzyme lipoprotein lipase, which plays a key role in the intravascular lipolysis of triglycerides present in some lipoprotein classes. This review focuses on the role of ANGPTL3 as emerged from the study of genetic variants of Angptl3 gene in mice and humans. Both loss of function genetic variants and inactivation of Angptl3 gene in mice are associated with a marked reduction of plasma levels of triglyceride and cholesterol and an increased activity of lipoprotein lipase and endothelial lipase. In humans with ANGPTL3 deficiency, caused by homozygous loss of function (LOF) variants of Angptl3 gene, the levels of all plasma lipoproteins are greatly reduced. This plasma lipid disorder referred to as familial combined hypolipidemia (FHBL2) does not appear to be associated with distinct pathological manifestations. Heterozygous carriers of LOF variants have reduced plasma levels of total cholesterol and triglycerides and are at lower risk of developing atherosclerotic cardiovascular disease, as compared to non-carriers. These observations have paved the way to the development of strategies to reduce the plasma level of atherogenic lipoproteins in man by the inactivation of ANGPTL3, using either a specific monoclonal antibody or anti-sense oligonucleotides.
2019
33
2
73
81
Angiopoietin-like protein 3 (ANGPTL3) deficiency and familial combined hypolipidemia / Tarugi, P.; Bertolini, S.; Calandra, S.. - In: JOURNAL OF BIOMEDICAL RESEARCH. - ISSN 1674-8301. - 33:2(2019), pp. 73-81. [10.7555/JBR.32.20170114]
Tarugi, P.; Bertolini, S.; Calandra, S.
File in questo prodotto:
File Dimensione Formato  
Angiopoietin-like+protein+3+(ANGPTL3)+deficiency+and+familial+combined+hypolipidemia.pdf

Open access

Tipologia: Versione pubblicata dall'editore
Dimensione 590.31 kB
Formato Adobe PDF
590.31 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11380/1195292
Citazioni
  • ???jsp.display-item.citation.pmc??? 9
  • Scopus 24
  • ???jsp.display-item.citation.isi??? 18
social impact