Evidence map›Paper›PMID 36263780›Full record

ArticleCirculation research2022

Proprotein Convertase Subtilisin/Kexin 9 (PCSK9) Promotes Macrophage Activation via LDL Receptor-Independent Mechanisms.

Shunsuke Katsuki, Prabhash K Jha, Adrien Lupieri, Toshiaki Nakano, Livia S A Passos, Maximillian A Rogers, Dakota Becker-Greene, Thanh-Dat Le, Julius L Decano, Lang Ho Lee and 14 more

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

Article in Circulation research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed, 1 pooled it
13.9field-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

47 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Article
  6. PCSK9 in critical illness - It's not all about lipids.Annals of clinical biochemistry · 2026
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. CRISPR-Cas9 Targeting PCSK9: A Promising Therapeutic Approach for Atherosclerosis.Journal of cardiovascular translational research · 2025
    Review
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors at 4 institutions in 3 countries.

Shunsuke Katsuki *The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0001-7851-216X
Prabhash K Jha *The Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Adrien LupieriThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0002-9245-0169
Toshiaki NakanoThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0001-9235-5615
Livia S A PassosThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0001-9888-6206
Maximillian A RogersThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Dakota Becker-GreeneThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Thanh-Dat LeThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Julius L DecanoThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).ORCID 0000-0003-0388-3585
Lang Ho LeeThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).ORCID 0000-0002-9684-160X
Gabriel C GuimaraesThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Ilyes AbdelhamidThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Arda HaluThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).ORCID 0000-0001-6217-790X
Alessandro MuscoloniThe Biomedical Cybernetics Group, Biotechnology Center, Center for Molecular and Cellular Bioengineering, Center for Systems Biology Dresden, Cluster of Excellence Physics of Life, Department of Physics, Technical University Dresden, Dresden, Germany (A.M., C.V.C).
Carlo V CannistraciThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Hideyuki HigashiThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Hengmin ZhangThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Amélie VrommanThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).
Peter LibbyThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0002-1502-502X
C Keith OzakiCenter for Complex Network Intelligence at the Tsinghua Laboratory of Brain and Intelligence, Department of Bioengineering, Tsinghua University, Beijing, China (A.M., C.V.C.).ORCID 0000-0001-9906-6218
Amitabh SharmaThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).
Sasha A SinghThe Center for Interdisciplinary Cardiovascular Sciences, Cardiovascular Division (M.A.R., J.L.D., L.H.L., I.A., A.H., H.H., H.Z., A.S., S.A.S., E.A., M.A.).ORCID 0000-0003-0929-3164
Elena AikawaThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0001-7835-2135
Masanori AikawaThe Center for Excellence in Vascular Biology, Cardiovascular Division (S.K., P.K.J., A.L., T.N., L.S.A.P., D.B.-G., T.-D.L., G.C.G., A.V., P.L., E.A., M.A.).ORCID 0000-0002-9275-2079
Center for Excellence in Education · USBrigham and Women's Hospital · USCenter for Systems Biology Dresden · DETsinghua University · CN

Funding

Improving Mitral Compensation In Ischemic RegurgitationR01HL141917 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI AIKAWA, ELENA, BISCHOFF, JOYCE E. · 2018 to 2021
$5.6M
Pro-inflammatory activation of human macrophages regulated by lncRNAsR01HL149302 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, MASANORI · 2019 to 2022
$2.9M
Macrophage-derived microcalcificaitonsR01HL136431 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2017 to 2020
$2.7M
PARP9 and PARP14 in atherosclerosisR01HL126901 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, MASANORI · 2016 to 2019
$2.4M
New driver of fibrosis and calcification in CAVDR01HL147095 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI AIKAWA, ELENA · 2019 to 2022
$2.4M
NHLBI NIH HHS R01 HL126901NHLBI NIH HHS R01 HL136431NHLBI NIH HHS R01 HL141917NHLBI NIH HHS R01 HL147095NHLBI NIH HHS R01 HL149302
6 · The paper itself

Abstract

backgroundActivated macrophages contribute to the pathogenesis of vascular disease. Vein graft failure is a major clinical problem with limited therapeutic options. PCSK9 (proprotein convertase subtilisin/kexin 9) increases low-density lipoprotein (LDL)-cholesterol levels via LDL receptor (LDLR) degradation. The role of PCSK9 in macrophage activation and vein graft failure is largely unknown, especially through LDLR-independent mechanisms. This study aimed to explore a novel mechanism of macrophage activation and vein graft disease induced by circulating PCSK9 in an LDLR-independent fashion.

methodsWe used

resultsIn

conclusionsCirculating PCSK9 induces macrophage activation and vein graft lesion development via LDLR-independent mechanisms. PCSK9 may be a potential target for pharmacologic treatment for this unmet medical need.

Indexed as

Macrophage ActivationProprotein Convertase 9AnimalsCholesterolLipoproteins, LDLMiceNF-kappa BReceptors, LDLSerine EndopeptidasesSubtilisinsCholesterolLipoproteins, LDLNF-kappa BPcsk9 protein, mouseProprotein Convertase 9Receptors, LDLSerine EndopeptidasesSubtilisinsgraft occlusion, vascularinflammationmacrophage activationreceptors, LDLsystems biology

Identifiers

PMID36263780
PMCPMC9973449
OpenAlexW4306867657

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.