Evidence map›Paper›PMID 27121620›Full record

ArticleCirculation research2016

PCSK9 Association With Lipoprotein(a).

Hagai Tavori, Devon Christian, Jessica Minnier, Deanna Plubell, Michael D Shapiro, Calvin Yeang, Ilaria Giunzioni, Mikael Croyal, P Barton Duell, Gilles Lambert and 2 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed, 1 pooled it
16.0field-weighted citation impact, top 1% of its field
1 · What the graph read from 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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

44 citing papers in PubMed, 1 synthesis or guideline pooled it, 108 citations in OpenAlex.

  1. Guideline
  2. Trial
  3. Article
  4. Journal of clinical and translational hepatology · 2025
    Article
  5. CRISPR-Cas9 Targeting PCSK9: A Promising Therapeutic Approach for Atherosclerosis.Journal of cardiovascular translational research · 2025
    Review
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 3 institutions in 2 countries.

Hagai TavoriFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.). fazio@ohsu.edu tavori@ohsu.edu.
Devon ChristianFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Jessica MinnierFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Deanna PlubellFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Michael D ShapiroFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Calvin YeangFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Ilaria GiunzioniFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Mikael CroyalFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
P Barton DuellFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Gilles LambertFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Sotirios TsimikasFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.).
Sergio FazioFrom the Department of Medicine, Center for Preventive Cardiology, Knight Cardiovascular Institute, Portland, OR (H.T., D.C., D.P., M.D.S., I.G., P.B.D., S.F.); School of Public Health, Oregon Health and Science University, Portland (J.M.); Sulpizio Cardiovascular Center, Vascular Medicine Program, University of California at San Diego, La Jolla (C.Y., S.T.); Inra UMR1280, Université de Nantes, CHU Hôtel-Dieu, Nantes, France (M.C., G.L.); Inserm UMR 1188, Sainte-Clotilde, France (G.L.); Université de la Réunion, Faculté de Médecine, Saint-Denis, France (G.L.); and CHU de la Réunion, Saint-Denis, France (G.L.). fazio@ohsu.edu tavori@ohsu.edu.
Oregon Health & Science University · USUniversity of California, San Diego · USInserm · FR

Funding

Blood Cells in Hemostasis and ThrombosisT32HL086344 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GINSBERG, MARK HOWARD · 2008 to 2023
$4.4M
Functional and structural correlates of PCSK9 association with lipoproteinsR01HL132985 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI PAMIR, NATHALIE · 2016 to 2024
$4.2M
Oxidation-specific nanoparticles for imaging atherosclerosisR01HL119828 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI TSIMIKAS, SOTIRIOS · 2013 to 2017
$2.0M
PCSK9, Lipoprotein receptors, and AtherosclerosisR01HL106845 · NHLBI · VANDERBILT UNIVERSITY · PI FAZIO, SERGIO · 2011 to 2014
$2.0M
NHLBI NIH HHS R01 HL106845NHLBI NIH HHS R01 HL119828NHLBI NIH HHS R01 HL132985NHLBI NIH HHS T32 HL086344
6 · The paper itself

Abstract

rationaleLipoprotein(a) [Lp(a)] is a highly atherogenic low-density lipoprotein-like particle characterized by the presence of apoprotein(a) [apo(a)] bound to apolipoprotein B. Proprotein convertase subtilisin/kexin type 9 (PCSK9) selectively binds low-density lipoprotein; we hypothesized that it can also be associated with Lp(a) in plasma.

objectiveCharacterize the association of PCSK9 and Lp(a) in 39 subjects with high Lp(a) levels (range 39-320 mg/dL) and in transgenic mice expressing either human apo(a) only or human Lp(a) (via coexpression of human apo(a) and human apolipoprotein B). METHODS AND

resultsWe show that PCSK9 is physically associated with Lp(a) in vivo using 3 different approaches: (1) analysis of Lp(a) fractions isolated by ultracentrifugation; (2) immunoprecipitation of plasma using antibodies to PCSK9 and immunodetection of apo(a); (3) ELISA quantification of Lp(a)-associated PCSK9. Plasma PCSK9 levels correlated with Lp(a) levels, but not with the number of kringle IV-2 repeats. PCSK9 did not bind to apo(a) only, and the association of PCSK9 with Lp(a) was not affected by the loss of the apo(a) region responsible for binding oxidized phospholipids. Preferential association of PCSK9 with Lp(a) versus low-density lipoprotein (1.7-fold increase) was seen in subjects with high Lp(a) and normal low-density lipoprotein. Finally, Lp(a)-associated PCSK9 levels directly correlated with plasma Lp(a) levels but not with total plasma PCSK9 levels.

conclusionsOur results show, for the first time, that plasma PCSK9 is found in association with Lp(a) particles in humans with high Lp(a) levels and in mice carrying human Lp(a). Lp(a)-bound PCSK9 may be pursued as a biomarker for cardiovascular risk.

Indexed as

AnimalsApolipoproteins AApolipoproteins BBiomarkersHumansLipoprotein(a)MiceProprotein Convertase 9Protein BindingApolipoproteins AApolipoproteins BBiomarkersLipoprotein(a)PCSK9 protein, humanProprotein Convertase 9lipids and lipoprotein metabolismlipoprotein(a)low-density lipoproteinproprotein convertase subtilisin/Kexin type 9

Identifiers

PMID27121620
PMCPMC4920709
OpenAlexW2344763201

What OpenQuestion holds

Textmetadata
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Read underepoch 390

Registered trials

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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.