ArticleCardiovascular research2016
Stable liver-specific expression of human IDOL in humanized mice raises plasma cholesterol.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 12 citations in OpenAlex.
- The Progression of Treatment for Refractory Hypercholesterolemia: Focus on the Prospect of Gene Therapy.Frontiers in genetics · 2022Review
- Idol Depletion Protects against Spontaneous Atherosclerosis in a Hamster Model of Familial Hypercholesterolemia.Oxidative medicine and cellular longevity · 2022Article
- MMAB promotes negative feedback control of cholesterol homeostasis.Nature communications · 2021Article
- The Cholesterol-Modulating Effect of Methanol Extract of Pigeon Pea (Molecules (Basel, Switzerland) · 2019Article
- An APOO Pseudogene on Chromosome 5q Is Associated With Low-Density Lipoprotein Cholesterol Levels.Circulation · 2018Article
- A Novel Type 2 Diabetes Mouse Model of Combined Diabetic Kidney Disease and Atherosclerosis.The American journal of pathology · 2018Article
- Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management.Frontiers in pharmacology · 2018Review
- A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.Nature medicine · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
aimsIDOL (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. METHODS AND
resultsUsing 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.
conclusionIn 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.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.