E-viri
Recenzirano
Odprti dostop
-
Ibrahim, Salam; Somanathan, Suryanarayan; Billheimer, Jeffrey; Wilson, James M; Rader, Daniel J
Cardiovascular research, 05/2016, Letnik: 110, Številka: 1Journal Article
IDOL (inducible degrader of the low-density lipoprotein receptor, LDLR) is an E3 ubiquitin ligase that promotes the ubiquitination and degradation of the LDLR. IDOL is a potential therapeutic target for the development of a novel class of low-density lipoprotein cholesterol (LDL-C)-lowering therapies. In an attempt to develop a mouse model for testing IDOL inhibitors, we examined the effects of adeno-associated virus (AAV)-mediated stable expression of human IDOL in the livers of mice 'humanized' with regard to lipoprotein metabolism. Using a liver-specific AAV serotype 8 (AAV8)-mediated delivery, AAV-hIDOL produced a dose-dependent increase in LDL-C levels and a decrease in liver LDLR protein. Furthermore, we expressed hIDOL in a 'humanized' mouse model of heterozygous familial hypercholesterolaemia (LDLR(+/-)/Apobec1(-/-)/hApoB-Tg, LAhB). In this model, total cholesterol (TC) and LDL-C levels were increased by ∼60% starting from 1 week and were sustainable for at least 3 weeks post-injection. Finally, we demonstrate that the effects caused by hIDOL expression are LDLR- dependent given the unchanged plasma lipids in LAhB mice lacking LDLR. In conclusion, our study demonstrates a dose-dependent physiological effect of human IDOL on LDL metabolism in mice. This provides a potential model for preclinical testing of IDOL inhibitors for reduction of LDL-C levels.
![loading ... loading ...](themes/default/img/ajax-loading.gif)
Vnos na polico
Trajna povezava
- URL:
Faktor vpliva
Dostop do baze podatkov JCR je dovoljen samo uporabnikom iz Slovenije. Vaš trenutni IP-naslov ni na seznamu dovoljenih za dostop, zato je potrebna avtentikacija z ustreznim računom AAI.
Leto | Faktor vpliva | Izdaja | Kategorija | Razvrstitev | ||||
---|---|---|---|---|---|---|---|---|
JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
Baze podatkov, v katerih je revija indeksirana
Ime baze podatkov | Področje | Leto |
---|
Povezave do osebnih bibliografij avtorjev | Povezave do podatkov o raziskovalcih v sistemu SICRIS |
---|
Vir: Osebne bibliografije
in: SICRIS
To gradivo vam je dostopno v celotnem besedilu. Če kljub temu želite naročiti gradivo, kliknite gumb Nadaljuj.