ANGPTL3 impacts proteinuria and hyperlipidemia in primary nephrotic syndrome.
ANGPTL3
Hyperlipidemia
Nephrotic syndrome
Proteinuria
Journal
Lipids in health and disease
ISSN: 1476-511X
Titre abrégé: Lipids Health Dis
Pays: England
ID NLM: 101147696
Informations de publication
Date de publication:
10 Apr 2022
10 Apr 2022
Historique:
received:
24
10
2021
accepted:
02
02
2022
entrez:
11
4
2022
pubmed:
12
4
2022
medline:
13
4
2022
Statut:
epublish
Résumé
It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.
Sections du résumé
BACKGROUND
BACKGROUND
It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development.
METHODS
METHODS
We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis.
RESULTS
RESULTS
Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS.
CONCLUSIONS
CONCLUSIONS
ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.
Identifiants
pubmed: 35399079
doi: 10.1186/s12944-022-01632-y
pii: 10.1186/s12944-022-01632-y
pmc: PMC8996604
doi:
Substances chimiques
ANGPTL3 protein, human
0
Angiopoietin-Like Protein 3
0
Angptl3 protein, mouse
0
Lipopolysaccharides
0
Triglycerides
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
38Subventions
Organisme : National Natural Science Foundation of China
ID : 81660130
Organisme : Natural Science Foundation of Gansu Province, China
ID : 18JR3RA045
Organisme : Science and Technology Program of Guangzhou, China
ID : 202102010222
Informations de copyright
© 2022. The Author(s).
Références
Intern Emerg Med. 2019 Jun;14(4):621-625
pubmed: 30929131
J Cell Commun Signal. 2013 Mar;7(1):49-60
pubmed: 23161414
Curr Opin Cell Biol. 2003 Oct;15(5):572-82
pubmed: 14519392
J Am Soc Nephrol. 2003 May;14(5):1200-11
pubmed: 12707390
J Lipid Res. 2020 Aug;61(8):1203-1220
pubmed: 32487544
Acute Med. 2018;17(1):36-43
pubmed: 29589604
Nat Genet. 2002 Feb;30(2):151-7
pubmed: 11788823
BMC Nephrol. 2015 Mar 29;16:38
pubmed: 25884163
Eur J Prev Cardiol. 2020 Dec;27(19):2251-2254
pubmed: 31648549
J Lipid Res. 2003 Aug;44(8):1552-8
pubmed: 12777470
Kidney Int. 2016 Jul;90(1):41-52
pubmed: 27165836
Pediatr Nephrol. 2013 Nov;28(11):2079-88
pubmed: 23250714
Biochem Biophys Res Commun. 2010 Aug 13;399(1):31-6
pubmed: 20633534
Lancet. 2003 Aug 23;362(9384):629-39
pubmed: 12944064
J Cardiovasc Med (Hagerstown). 2021 Mar 1;22(3):151-161
pubmed: 32858625
Proc Natl Acad Sci U S A. 2018 Feb 6;115(6):E1249-E1258
pubmed: 29358393
J Biol Chem. 2007 Jan 5;282(1):467-77
pubmed: 17082197
BMC Nephrol. 2019 May 24;20(1):185
pubmed: 31126248
Kidney Res Clin Pract. 2012 Jun;31(2):87-93
pubmed: 26889414
Cell Stem Cell. 2013 Dec 5;13(6):659-62
pubmed: 24315440
Pediatr Res. 2015 Jun;77(6):732-9
pubmed: 25710887
Int J Mol Sci. 2021 Jan 13;22(2):
pubmed: 33451033
Endocrine. 2016 May;52(2):187-93
pubmed: 26754661
J Lipid Res. 2016 Jun;57(6):1097-107
pubmed: 27040449
Science. 2013 Feb 15;339(6121):819-23
pubmed: 23287718
J Clin Invest. 2004 May;113(10):1390-7
pubmed: 15146236
Nat Rev Endocrinol. 2017 Dec;13(12):731-739
pubmed: 28984319
Sci Rep. 2018 Apr 30;8(1):6752
pubmed: 29713054