ArticleJournal of lipid research2015
PCSK9 deficiency unmasks a sex- and tissue-specific subcellular distribution of the LDL and VLDL receptors in mice.
Article in Journal of lipid research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 59 citations in OpenAlex.
- Gender differences in the plasma profiles of proprotein convertase subtilisin/kexin-type 9 (PCSK9), soluble low-density lipoprotein receptor (sLDLR), total cholesterol, and triglycerides in patients with colorectal cancer liver metastases: diagnostic and prognostic implications.Lipids in health and disease · 2026Article
- Reduced Growth and Inflammation in Lrp5Journal of cellular and molecular medicine · 2025Article
- PCSK9 deficiency promotes the development of peripheral neuropathy.JCI insight · 2025Article
- Pleiotropic Effects of PCSK9 Inhibitors on Cardio-Cerebrovascular Diseases.Biomedicines · 2024Review
- Lipoprotein Metabolism, Dyslipidemia, and Lipid-Lowering Therapy in Women: A Comprehensive Review.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Proprotein convertase subtilisin/kexin type 9 deficiency in extrahepatic tissues: emerging considerations.Frontiers in pharmacology · 2024Review
- LDL lowering effect of PCSK9 inhibition is reduced in women.European heart journal. Cardiovascular pharmacotherapy · 2023Article
- A bibliometric analysis of PCSK9 inhibitors from 2007 to 2022.Frontiers in endocrinology · 2023Article
- Rosa26-LSL-dCas9-VPR: a versatile mouse model for tissue specific and simultaneous activation of multiple genes for drug discovery.Scientific reports · 2022Article
- Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Deletion but Not Inhibition of Extracellular PCSK9 Reduces Infarct Sizes Ex Vivo but Not In Vivo.International journal of molecular sciences · 2022Article
- The Multifaceted Biology of PCSK9.Endocrine reviews · 2022Review
- Sex difference in circulating PCSK9 and its clinical implications.Frontiers in pharmacology · 2022Review
- Downregulation of low-density lipoprotein receptor mRNA in lymphatic endothelial cells impairs lymphatic function through changes in intracellular lipids.Theranostics · 2022Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Characterization of the CDAA Diet-Induced Non-alcoholic Steatohepatitis Model: Sex-Specific Differences in Inflammation, Fibrosis, and Cholesterol Metabolism in Middle-Aged Mice.Frontiers in physiology · 2021Article
- Sex-Specific Association of Endogenous PCSK9 With Memory Function in Elderly Subjects at High Cardiovascular Risk.Frontiers in aging neuroscience · 2021Article
- Research progress on alternative non-classical mechanisms of PCSK9 in atherosclerosis in patients with and without diabetes.Cardiovascular diabetology · 2020Review
- Development of a Predictive Model to Induce Atherogenesis and Hepato-Renal Impairment in Female Rats.Biomolecules · 2019Article
- Ser-Phosphorylation of PCSK9 (Proprotein Convertase Subtilisin-Kexin 9) by Fam20C (Family With Sequence Similarity 20, Member C) Kinase Enhances Its Ability to Degrade the LDLR (Low-Density Lipoprotein Receptor).Arteriosclerosis, thrombosis, and vascular biology · 2019Article
- PCSK9 is Expressed in Human Visceral Adipose Tissue and Regulated by Insulin and Cardiac Natriuretic Peptides.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Proprotein convertase subtilisin kexin type 9 (PCSK9), the last member of the family of Proprotein Convertases related to Subtilisin and Kexin, regulates LDL-cholesterol by promoting the endosomal/lysosomal degradation of the LDL receptor (LDLR). Herein, we show that the LDLR cell surface levels dramatically increase in the liver and pancreatic islets of PCSK9 KO male but not female mice. In contrast, in KO female mice, the LDLR is more abundant at the cell surface enterocytes, as is the VLDL receptor (VLDLR) at the cell surface of adipocytes. Ovariectomy of KO female mice led to a typical KO male pattern, whereas 17β-estradiol (E2) treatment restored the female pattern without concomitant changes in LDLR adaptor protein 1 (also known as ARH), disabled-2, or inducible degrader of the LDLR expression levels. We also show that this E2-mediated regulation, which is observed only in the absence of PCSK9, is abolished upon feeding the mice a high-cholesterol diet. The latter dramatically represses PCSK9 expression and leads to high surface levels of the LDLR in the hepatocytes of all sexes and genotypes. In conclusion, the absence of PCSK9 results in a sex- and tissue-specific subcellular distribution of the LDLR and VLDLR, which is determined by E2 levels.
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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.