ArticlePloS one2012
Annexin A2 is a natural extrahepatic inhibitor of the PCSK9-induced LDL receptor degradation.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 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
56 citing papers in PubMed, 122 citations in OpenAlex.
- Annexin A2 Is Associated with Dietary Cholesterol-Induced Metabolic Dysregulation and the Progression of Hepatic Fibrosis.Metabolites · 2026Article
- Leveraging large-scale biobanks for therapeutic target discovery.HGG advances · 2026Article
- PCSK9 and Lipid Metabolism: Genetic Variants, Current Therapies, and Cardiovascular Outcomes.Cardiovascular drugs and therapy · 2025Review
- Review
- PCSK9 deficiency promotes the development of peripheral neuropathy.JCI insight · 2025Article
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- The multifaceted role of PCSK9 in cancer pathogenesis, tumor immunity, and immunotherapy.Medical oncology (Northwood, London, England) · 2024Review
- Tale of two systems: the intertwining duality of fibrinolysis and lipoprotein metabolism.Journal of thrombosis and haemostasis : JTH · 2023Review
- The evolving landscape of PCSK9 inhibition in cancer.European journal of pharmacology · 2023Review
- Testosterone Coordinates Gene Expression Across Different Tissues to Produce Carotenoid-Based Red Ornamentation.Molecular biology and evolution · 2023Article
- High fat diet and PCSK9 knockout modulates lipid profile of the liver and changes the expression of lipid homeostasis related genes.Nutrition & metabolism · 2023Article
- Review
- A Temporal Comparative RNA Transcriptome Profile of the Annexin Gene Family in the Salivary versus Lacrimal Glands of the Sjögren's Syndrome-Susceptible C57BL/6.NOD-International journal of molecular sciences · 2022Article
- Proteomics research of SARS-CoV-2 and COVID-19 disease.Medical review (2021) · 2022Review
- Article
- Emerging Insights on the Diverse Roles of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) in Chronic Liver Diseases: Cholesterol Metabolism and Beyond.International journal of molecular sciences · 2022Review
- Unconventional Protein Secretion in Brain Tumors Biology: Enlightening the Mechanisms for Tumor Survival and Progression.Frontiers in cell and developmental biology · 2022Review
- Differential proteomic analysis of mouse cerebrums with high-fat diet (HFD)-induced hyperlipidemia.PeerJ · 2022Article
- Physical activity to reduce PCSK9 levels.Frontiers in cardiovascular medicine · 2022Review
- Annexins and cardiovascular diseases: Beyond membrane trafficking and repair.Frontiers in cell and developmental biology · 2022Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
Abstract
Proprotein convertase subtilisin/kexin-9 (PCSK9) enhances the degradation of hepatic low-density lipoprotein receptor (LDLR). Deletion of PCSK9, and loss-of-function mutants in humans result in lower levels of circulating LDL-cholesterol and a strong protection against coronary heart disease. Accordingly, the quest for PCSK9 inhibitors has major clinical implications. We have previously identified annexin A2 (AnxA2) as an endogenous binding partner and functional inhibitor of PCSK9. Herein, we studied the relevance of AnxA2 in PCSK9 inhibition and lipid metabolism in vivo. Plasma analyses of AnxA2(-/-) mice revealed: i) a ∼1.4-fold increase in LDL-cholesterol without significant changes in VLDLs or HDLs, and ii) a ∼2-fold increase in circulating PCSK9 levels. Western blotting and immunohistochemistry of AnxA2(-/-) tissues revealed that the LDLR was decreased by ∼50% in extrahepatic tissues, such as adrenals and colon. We also show that AnxA2-derived synthetic peptides block the PCSK9≡LDLR interaction in vitro, and adenoviral overexpression of AnxA2 in mouse liver increases LDLR protein levels in vivo. These results suggest that AnxA2 acts as an endogenous regulator of LDLR degradation, mostly in extrahepatic tissues. Finally, we identified an AnxA2 coding polymorphism, V98L, that correlates with lower circulating levels of PCSK9 thereby extending our results on the physiological role of AnxA2 in humans.
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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.