ArticleJournal of lipid research2016
Dose-dependent effects of siRNA-mediated inhibition of SCAP on PCSK9, LDLR, and plasma lipids in mouse and rhesus monkey.
Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- De novo lipogenesis is essential for platelet production in humans.Nature metabolism · 2020Trial
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- A cholesterol-binding bacterial toxin provides a strategy for identifying a specific Scap inhibitor that blocks lipid synthesis in animal cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Hepatic SREBP signaling requires SPRING to govern systemic lipid metabolism in mice and humans.Nature communications · 2023Article
- Caffeine blocks SREBP2-induced hepatic PCSK9 expression to enhance LDLR-mediated cholesterol clearance.Nature communications · 2022Article
- Nanobiotechnology approaches for cardiovascular diseases: site-specific targeting of drugs and nanoparticles for atherothrombosis.Journal of nanobiotechnology · 2022Review
- Phytogenic Water Additives Improve Broiler Growth Performance via Modulation of Intermediary Metabolism-Related Signaling Pathways.Animals : an open access journal from MDPI · 2021Article
- Phytogenic feed additives improve broiler feed efficiency via modulation of intermediary lipid and protein metabolism-related signaling pathways.Poultry science · 2021Article
- Introducing an In Vitro Liver Stability Assay Capable of Predicting the In Vivo Pharmacodynamic Efficacy of siRNAs for IVIVC.Molecular therapy. Nucleic acids · 2020Article
- Diet-induced hepatic steatosis abrogates cell-surface LDLR by inducingThe Journal of biological chemistry · 2019Article
- Developmental and extrahepatic physiological functions of SREBP pathway genes in mice.Seminars in cell & developmental biology · 2018Review
- New insights into ANGPLT3 in controlling lipoprotein metabolism and risk of cardiovascular diseases.Lipids in health and disease · 2018Review
- Cholesterol auxotrophy and intolerance to ezetimibe in mice with SREBP-2 deficiency in the intestine.Journal of lipid research · 2017Article
- Physiological and therapeutic regulation of PCSK9 activity in cardiovascular disease.Basic research in cardiology · 2017Review
Corrections and comments
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Authors and funding
22 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SREBP cleavage-activating protein (SCAP) is a key protein in the regulation of lipid metabolism and a potential target for treatment of dyslipidemia. SCAP is required for activation of the transcription factors SREBP-1 and -2. SREBPs regulate the expression of genes involved in fatty acid and cholesterol biosynthesis, and LDL-C clearance through the regulation of LDL receptor (LDLR) and PCSK9 expression. To further test the potential of SCAP as a novel target for treatment of dyslipidemia, we used siRNAs to inhibit hepatic SCAP expression and assess the effect on PCSK9, LDLR, and lipids in mice and rhesus monkeys. In mice, robust liver Scap mRNA knockdown (KD) was achieved, accompanied by dose-dependent reduction in SREBP-regulated gene expression, de novo lipogenesis, and plasma PCSK9 and lipids. In rhesus monkeys, over 90% SCAP mRNA KD was achieved resulting in approximately 75, 50, and 50% reduction of plasma PCSK9, TG, and LDL-C, respectively. Inhibition of SCAP function was demonstrated by reduced expression of SREBP-regulated genes and de novo lipogenesis. In conclusion, siRNA-mediated inhibition of SCAP resulted in a significant reduction in circulating PCSK9 and LDL-C in rodent and primate models supporting SCAP as a novel target for the treatment of dyslipidemia.
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Registered trials
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.