Sökning: id:"swepub:oai:prod.swepub.kib.ki.se:145465654" >
3-Hydroxyanthralini...
-
Berg, MKarolinska Institutet
(författare)
3-Hydroxyanthralinic acid metabolism controls the hepatic SREBP/lipoprotein axis, inhibits inflammasome activation in macrophages, and decreases atherosclerosis in Ldlr-/- mice
- Artikel/kapitelEngelska2020
Förlag, utgivningsår, omfång ...
-
2019-10-07
-
Oxford University Press (OUP),2020
Nummerbeteckningar
-
LIBRIS-ID:oai:prod.swepub.kib.ki.se:145465654
-
http://kipublications.ki.se/Default.aspx?queryparsed=id:145465654URI
-
https://doi.org/10.1093/cvr/cvz258DOI
Kompletterande språkuppgifter
-
Språk:engelska
-
Sammanfattning på:engelska
Ingår i deldatabas
Klassifikation
-
Ämneskategori:ref swepub-contenttype
-
Ämneskategori:art swepub-publicationtype
Anmärkningar
-
AimsAtherosclerosis is a chronic inflammatory disease involving immunological and metabolic processes. Metabolism of tryptophan (Trp) via the kynurenine pathway has shown immunomodulatory properties and the ability to modulate atherosclerosis. We identified 3-hydroxyanthranilic acid (3-HAA) as a key metabolite of Trp modulating vascular inflammation and lipid metabolism. The molecular mechanisms driven by 3-HAA in atherosclerosis have not been completely elucidated. In this study, we investigated whether two major signalling pathways, activation of SREBPs and inflammasome, are associated with the 3-HAA-dependent regulation of lipoprotein synthesis and inflammation in the atherogenesis process. Moreover, we examined whether inhibition of endogenous 3-HAA degradation affects hyperlipidaemia and plaque formation.Methods and resultsIn vitro, we showed that 3-HAA reduces SREBP-2 expression and nuclear translocation and apolipoprotein B secretion in HepG2 cell cultures, and inhibits inflammasome activation and IL-1β production by macrophages. Using Ldlr−/− mice, we showed that inhibition of 3-HAA 3,4-dioxygenase (HAAO), which increases the endogenous levels of 3-HAA, decreases plasma lipids and atherosclerosis. Notably, HAAO inhibition led to decreased hepatic SREBP-2 mRNA levels and lipid accumulation, and improved liver pathology scores.ConclusionsWe show that the activity of SREBP-2 and the inflammasome can be regulated by 3-HAA metabolism. Moreover, our study highlights that targeting HAAO is a promising strategy to prevent and treat hypercholesterolaemia and atherosclerosis.
Biuppslag (personer, institutioner, konferenser, titlar ...)
-
Polyzos, KA
(författare)
-
Agardh, H
(författare)
-
Baumgartner, RKarolinska Institutet
(författare)
-
Forteza, MJKarolinska Institutet
(författare)
-
Kareinen, I
(författare)
-
Gistera, AKarolinska Institutet
(författare)
-
Bottcher, G
(författare)
-
Hurt-Camejo, E
(författare)
-
Hansson, GKKarolinska Institutet
(författare)
-
Ketelhuth, DFJKarolinska Institutet
(författare)
-
Karolinska Institutet
(creator_code:org_t)
Sammanhörande titlar
-
Ingår i:Cardiovascular research: Oxford University Press (OUP)116:12, s. 1948-19571755-32450008-6363
Internetlänk
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Berg, M
-
Polyzos, KA
-
Agardh, H
-
Baumgartner, R
-
Forteza, MJ
-
Kareinen, I
-
visa fler...
-
Gistera, A
-
Bottcher, G
-
Hurt-Camejo, E
-
Hansson, GK
-
Ketelhuth, DFJ
-
visa färre...
- Artiklar i publikationen
-
Cardiovascular r ...
- Av lärosätet
-
Karolinska Institutet