Evidence map›Paper›PMID 31092728›Full record

ArticleJCI insight2019

Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment.

Joost P Schanstra, Trang Td Luong, Manousos Makridakis, Sophie Van Linthout, Vasiliki Lygirou, Agnieszka Latosinska, Ioana Alesutan, Beate Boehme, Nadeshda Schelski, Dirk Von Lewinski and 13 more

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

17 citing papers in PubMed, 38 citations in OpenAlex.

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  9. Medial Arterial Calcification: JACC State-of-the-Art Review.Journal of the American College of Cardiology · 2021
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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

23 authors at 10 institutions in 6 countries.

Joost P SchanstraInstitute of Cardiovascular and Metabolic Disease, INSERM, Toulouse, France.
Trang Td LuongDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Manousos MakridakisBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Sophie Van LinthoutDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Vasiliki LygirouBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Agnieszka LatosinskaMosaiques Diagnostics GmbH, Hannover, Germany.
Ioana AlesutanDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Beate BoehmeDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Nadeshda SchelskiDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Dirk Von LewinskiDepartment of Cardiology, Medical University of Graz, Graz, Austria.
William MullenInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Stuart NicklinInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Christian DellesInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Guylène FeuilletInstitute of Cardiovascular and Metabolic Disease, INSERM, Toulouse, France.
Colette DenisInstitute of Cardiovascular and Metabolic Disease, INSERM, Toulouse, France.
Florian LangDepartment of Physiology I, University of Tubingen, Tubingen, Germany.
Burkert PieskeDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Jean-Loup BascandsINSERM, U1188, Université de La Réunion, Sainte-Clotilde, La Réunion, France.
Harald MischakMosaiques Diagnostics GmbH, Hannover, Germany.
Jean-Sebastien Saulnier-BlacheInstitute of Cardiovascular and Metabolic Disease, INSERM, Toulouse, France.
Jakob VoelklDepartment of Internal Medicine and Cardiology, Charité - Universitätsmedizin Berlin, Campus Virchow-Klinikum, Berlin, Germany.
Antonia VlahouBiotechnology Laboratory, Centre of Basic Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Julie KleinInstitute of Cardiovascular and Metabolic Disease, INSERM, Toulouse, France.
Université Toulouse III - Paul Sabatier · FRBiomedical Research Foundation of the Academy of Athens · GRCharité - Universitätsmedizin Berlin · DEUniversity of Glasgow · GBGerman Centre for Cardiovascular Research · DEJohannes Kepler University of Linz · ATMosaiques Diagnostics and Therapeutics (Germany) · DEInserm · FRMedical University of Graz · ATUniversity of Tübingen · DE

Funding

British Heart Foundation RE/13/5/30177
6 · The paper itself

Abstract

Although cardiovascular disease (CVD) is the leading cause of morbimortality worldwide, promising new drug candidates are lacking. We compared the arterial high-resolution proteome of patients with advanced versus early-stage CVD to predict, from a library of small bioactive molecules, drug candidates able to reverse this disease signature. Of the approximately 4000 identified proteins, 100 proteins were upregulated and 52 were downregulated in advanced-stage CVD. Arachidonyl trifluoromethyl ketone (AACOCF3), a cytosolic phospholipase A2 (cPLA2) inhibitor was predicted as the top drug able to reverse the advanced-stage CVD signature. Vascular cPLA2 expression was increased in patients with advanced-stage CVD. Treatment with AACOCF3 significantly reduced vascular calcification in a cholecalciferol-overload mouse model and inhibited osteoinductive signaling in vivo and in vitro in human aortic smooth muscle cells. In conclusion, using a systems biology approach, we have identified a potentially new compound that prevented typical vascular calcification in CVD in vivo. Apart from the clear effect of this approach in CVD, such strategy should also be able to generate novel drug candidates in other complex diseases.

Indexed as

Systems BiologyAdultAnimalsAntigens, Human PlateletApolipoproteins EArachidonic AcidsAtherosclerosisCardiovascular DiseasesCytosolDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLMice, KnockoutAntigens, Human PlateletApolipoproteins EArachidonic Acidsarachidonyltrifluoromethanehuman platelet antigen 1bAtherosclerosisCardiovascular diseaseVascular Biology

Identifiers

PMID31092728
PMCPMC6542631
OpenAlexW2944882061

What Socratic holds

Textmetadata
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.