ArticleCirculation2013
Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation.
Article in Circulation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 4 of them syntheses that pooled it.
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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
84 citing papers in PubMed, 4 syntheses or guidelines pooled it, 189 citations in OpenAlex.
- Effect of PCSK9 Monoclonal Antibody Versus Placebo/Ezetimibe on Atrial Fibrillation in Patients at High Cardiovascular Risk: A Meta-Analysis of 26 Randomized Controlled Trials.Cardiovascular drugs and therapy · 2023 · on this mapPooled it
- Does 24-h Activity Cycle Influence Plasma PCSK9 Concentration? A Systematic Review and Meta-Analysis.Current atherosclerosis reports · 2020Pooled it
- Pooled it
- Pooled it
- Thyroid hormone reduces PCSK9 and stimulates bile acid synthesis in humans.Journal of lipid research · 2014Trial
- Roles of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the regulation of hepatic triglyceride metabolism.Journal of lipid research · 2026Review
- Review
- The discovery of PCSK9 as a pivotal point in the prevention of cardiovascular disease.American journal of preventive cardiology · 2025Review
- Quercetin's regulation of glucose and lipid metabolism in gestational diabetes mellitus: role of the PCSK9/LDLR axis.Nutrition & metabolism · 2025Article
- LDL-Bound PCSK9 Has a Slower Clearance Kinetic and Higher Use for HSPGs Than Free-PCSK9-Brief Report.Arteriosclerosis, thrombosis, and vascular biology · 2025Article
- Prolonged fasting promotes systemic inflammation and platelet activation in humans: A medically supervised, water-only fasting and refeeding study.Molecular metabolism · 2025Article
- CRISPR-Cas9 Targeting PCSK9: A Promising Therapeutic Approach for Atherosclerosis.Journal of cardiovascular translational research · 2025Review
- Phenotypic heterogeneity in mortality and prognosis of pulmonary alveolar proteinosis: a large-scale, global pooled analysis of individual-level data.Orphanet journal of rare diseases · 2025Article
- PCSK9 in Vascular Aging and Age-Related Diseases.Aging and disease · 2025Review
- 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
- Cholesterol reduction by immunization with a PCSK9 mimic.Cell reports · 2024Article
- Atherosclerosis and Toll-Like Receptor4 (TLR4), Lectin-Like Oxidized Low-Density Lipoprotein-1 (LOX-1), and Proprotein Convertase Subtilisin/Kexin Type9 (PCSK9).Mediators of inflammation · 2024Review
- PCSK9i promoting the transformation of AS plaques into a stable plaque by targeting the miR-186-5p/Wipf2 and miR-375-3p/Pdk1/Yap1 in ApoE-/- mice.Frontiers in medicine · 2024Article
- Soluble PCSK9 Inhibition: Indications, Clinical Impact, New Molecular Insights and Practical Approach-Where Do We Stand?Journal of clinical medicine · 2023Review
- RNF130 Regulates LDLR Availability and Plasma LDL Cholesterol Levels.Circulation research · 2023Article
24 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundProprotein convertase subtilisin/kexin type 9 (PCSK9) modulates low-density lipoprotein (LDL) receptor (LDLR) degradation, thus influencing serum cholesterol levels. However, dysfunctional LDLR causes hypercholesterolemia without affecting PCSK9 clearance from the circulation. METHODS AND
resultsTo study the reciprocal effects of PCSK9 and LDLR and the resultant effects on serum cholesterol, we produced transgenic mice expressing human (h) PCSK9. Although hPCSK9 was expressed mainly in the kidney, LDLR degradation was more evident in the liver. Adrenal LDLR levels were not affected, likely because of the impaired PCSK9 retention in this tissue. In addition, hPCSK9 expression increased hepatic secretion of apolipoprotein B-containing lipoproteins in an LDLR-independent fashion. Expression of hPCSK9 raised serum murine PCSK9 levels by 4.3-fold in wild-type mice and not at all in LDLR(-/-) mice, in which murine PCSK9 levels were already 10-fold higher than in wild-type mice. In addition, LDLR(+/-) mice had a 2.7-fold elevation in murine PCSK9 levels and no elevation in cholesterol levels. Conversely, acute expression of human LDLR in transgenic mice caused a 70% decrease in serum murine PCSK9 levels. Turnover studies using physiological levels of hPCSK9 showed rapid clearance in wild-type mice (half-life, 5.2 minutes), faster clearance in human LDLR transgenics (2.9 minutes), and much slower clearance in LDLR(-/-) recipients (50.5 minutes). Supportive results were obtained with an in vitro system. Finally, up to 30% of serum hPCSK9 was associated with LDL regardless of LDLR expression.
conclusionsOur results support a scenario in which LDLR represents the main route of elimination of PCSK9 and a reciprocal regulation between these 2 proteins controls serum PCSK9 levels, hepatic LDLR expression, and serum LDL 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.