Evidence map›Paper›PMID 33432099›Full record

Observational studyScientific reports2021

Role of PAI-1 in hepatic steatosis and dyslipidemia.

Joshua A Levine, Carlota Oleaga, Mesut Eren, Ansel P Amaral, Meng Shang, Elizabeth Lux, Sadiya S Khan, Sanjiv J Shah, Yasuhiro Omura, Nathalie Pamir and 6 more

Open access · goldFull text readObservational Study
In one paragraph

Observational study in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
53citing papers in PubMed, 2 pooled it
12.7field-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

53 citing papers in PubMed, 2 syntheses or guidelines pooled it, 106 citations in OpenAlex.

  1. Pooled it
  2. Systematic Review and Meta-Analysis ofFrontiers in cardiovascular medicine · 2022
    Pooled it
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  17. Walking the VLDL tightrope in cardiometabolic diseases.Trends in endocrinology and metabolism: TEM · 2025
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 3 institutions in 2 countries.

Joshua A LevineDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Carlota OleagaCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Mesut ErenDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Ansel P AmaralDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Meng ShangDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Elizabeth LuxDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Sadiya S KhanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Sanjiv J ShahDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Yasuhiro OmuraDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Nathalie PamirCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Joshua HayCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Grant BarishDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA.
Toshio MiyataDepartment of Molecular Medicine and Therapy, United Centers for Advanced Research and Translational Medicine, Tohoku University Graduate School of Medicine, Miyagi, Japan.
Hagai TavoriCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Sergio FazioCenter for Preventive Cardiology, Knight Cardiovascular Institute, Oregon Health and Science University, Portland, OR, USA.
Douglas E VaughanDepartment of Medicine, Northwestern University Feinberg School of Medicine, Arkes Pavilion, Suite 2330, 676 N. St. Clair Street, Chicago, IL, 60611-2927, USA. d-vaughan@northwestern.edu.
Northwestern University · USOregon Health & Science University · USTohoku University · JP

Funding

Pleiotropic Role of PAI-1 in Cardiovascular AgingR01HL051387 · NHLBI · VANDERBILT UNIVERSITY · PI VAUGHAN, DOUGLAS E · 1994 to 2023
$7.9M
Functional and structural correlates of PCSK9 association with lipoproteinsR01HL132985 · NHLBI · OREGON HEALTH & SCIENCE UNIVERSITY · PI PAMIR, NATHALIE · 2016 to 2024
$4.2M
Northwestern University Molecular and Translational Cardiovascular Training ProgramT32HL134633 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MCNALLY, ELIZABETH M · 2017 to 2021
$1.6M
NHLBI NIH HHS R01 HL051387NHLBI NIH HHS R01 HL132985NHLBI NIH HHS T32 HL134633
6 · The paper itself

Abstract

Plasminogen activator inhibitor 1 (PAI-1) is a functional biomarker of the metabolic syndrome. Previous studies have demonstrated that PAI-1 is a mechanistic contributor to several elements of the syndrome, including obesity, hypertension and insulin resistance. Here we show that PAI-1 is also a critical regulator of hepatic lipid metabolism. RNA sequencing revealed that PAI-1 directly regulates the transcriptional expression of numerous genes involved in mammalian lipid homeostasis, including PCSK9 and FGF21. Pharmacologic or genetic reductions in plasma PAI-1 activity ameliorates hyperlipidemia in vivo. These experimental findings are complemented with the observation that genetic deficiency of PAI-1 is associated with reduced plasma PCSK9 levels in humans. Taken together, our findings identify PAI-1 as a novel contributor to mammalian lipid metabolism and provides a fundamental mechanistic insight into the pathogenesis of one of the most pervasive medical problems worldwide.

Indexed as

AnimalsCells, CulturedCohort StudiesDyslipidemiasFatty LiverFemaleFibroblast Growth FactorsHep G2 CellsHumansLipid MetabolismMaleMiceMice, Inbred C57BLMice, TransgenicPlasminogen Activator Inhibitor 1Proprotein Convertase 9FGF21 protein, humanFibroblast Growth FactorsPCSK9 protein, humanPlasminogen Activator Inhibitor 1Proprotein Convertase 9SERPINE1 protein, human

Identifiers

PMID33432099
PMCPMC7801442
OpenAlexW3118728355

What Socratic holds

Textfull text, public
LicenceCC BY
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 Socratic graph.