ArticleCardiovascular research2016
Human PCSK9 promotes hepatic lipogenesis and atherosclerosis development via apoE- and LDLR-mediated mechanisms.
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 58 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
58 citing papers in PubMed, 3 syntheses or guidelines pooled it, 107 citations in OpenAlex.
- Meta-GWAS of PCSK9 levels detects two novel loci at APOB and TM6SF2.Human molecular genetics · 2022Pooled it
- Does 24-h Activity Cycle Influence Plasma PCSK9 Concentration? A Systematic Review and Meta-Analysis.Current atherosclerosis reports · 2020Pooled it
- Pooled it
- Trial
- Roles of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the regulation of hepatic triglyceride metabolism.Journal of lipid research · 2026Review
- PROTAC-mediated PCSK9 degradation attenuates atherosclerosis and improves plaque composition via suppression of NF-κB/TNF-α pathway.BMC medicine · 2026Article
- Effects of hepatic lipid ratio on lipid metabolism indices and hepatic gene expression in late-phase laying hens.Poultry science · 2026Article
- Biomimetic nanocomplexes loading with evolocumab and curcumin for synergistic anti-atherosclerosis therapy in ApoEJournal of nanobiotechnology · 2025Article
- Review
- Silencing hepatic PCSK9 via novel chimeric AAV8 mitigates the progression of atherosclerosis by inhibiting inflammation in ApoEMolecular therapy. Methods & clinical development · 2025Article
- PCSK9 with a gain of function D374Y mutation aggravates atherosclerosis by inhibiting PPARα expression.Scientific reports · 2025Article
- The relationship between oxLDL, sLOX-1, PCSK9 and carotid intima-media thickness in patients with prediabetes and type 2 diabetes.Scientific reports · 2025Article
- Engineered extracellular vesicles as nanosponges for lysosomal degradation of PCSK9.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- PCSK9 Promotes Atherosclerotic Plaque Instability by Inducing VSMC Ferroptosis through the YAP1-NUPR1 Axis.Research (Washington, D.C.) · 2025Article
- PCSK9 and Coronary Artery Plaque-New Opportunity or Red Herring?Current atherosclerosis reports · 2024Review
- Stromal cell-derived factor-1 alpha improves cardiac function in a novel diet-induced coronary atherosclerosis model, the SR-B1ΔCT/LDLR KO mouse.Atherosclerosis · 2024Article
- Review
- The role of proprotein convertase subtilisin/kexin 9 (PCSK9) in macrophage activation: a focus on its LDL receptor-independent mechanisms.Frontiers in cardiovascular medicine · 2024Review
- Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
aimsProprotein convertase subtilisin/kexin type 9 (PCSK9) promotes the degradation of hepatic low-density lipoprotein (LDL) receptors (LDLR), thereby, decreasing hepatocyte LDL-cholesterol (LDL-C) uptake. However, it is unknown whether PCSK9 has effects on atherogenesis that are independent of lipid changes. The present study investigated the effect of human (h) PCSK9 on plasma lipids, hepatic lipogenesis, and atherosclerotic lesion size and composition in transgenic mice expressing hPCSK9 (hPCSK9tg) on wild-type (WT), LDLR⁻/⁻, or apoE⁻/⁻ background. METHODS AND
resultshPCSK9 expression significantly increased plasma cholesterol (+91%), triglycerides (+18%), and apoB (+57%) levels only in WT mice. The increase in plasma lipids was a consequence of both decreased hepatic LDLR and increased hepatic lipid production, mediated transcriptionally and post-transcriptionally by PCSK9 and dependent on both LDLR and apoE. Despite the lack of changes in plasma lipids in mice expressing hPCSK9 and lacking LDLR (the main target for PCSK9) or apoE (a canonical ligand for the LDLR), hPCSK9 expression increased aortic lesion size in the absence of apoE (268 655 ± 97 972 µm² in hPCSK9tg/apoE⁻/⁻ vs. 189 423 ± 65 700 µm(2) in apoE⁻/⁻) but not in the absence of LDLR. Additionally, hPCSK9 accumulated in the atheroma and increased lesion Ly6C(hi) monocytes (by 21%) in apoE⁻/⁻ mice, but not in LDLR⁻/⁻ mice.
conclusionsPCSK9 increases hepatic lipid and lipoprotein production via apoE- and LDLR-dependent mechanisms. However, hPCSK9 also accumulate in the artery wall and directly affects atherosclerosis lesion size and composition independently of such plasma lipid and lipoprotein changes. These effects of hPCSK9 are dependent on LDLR but are independent of apoE.
Indexed as
Identifiers
What OpenQuestion holds
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.