ArticleJCI insight2019
Systems biology identifies cytosolic PLA2 as a target in vascular calcification treatment.
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.
What it found
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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.
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Who cites it
17 citing papers in PubMed, 38 citations in OpenAlex.
- Calcium waves and nuclear tension changes coordinate mechanical stress dissipation in locally folded epithelia.iScience · 2026Article
- Research progress of cPLA2 in cardiovascular diseases (Review).Molecular medicine reports · 2025Review
- Lysophosphatidylcholine Impairs the Mitochondria Homeostasis Leading to Trophoblast Dysfunction in Gestational Diabetes Mellitus.Antioxidants (Basel, Switzerland) · 2024Article
- BRG1 is involved in vascular calcification in chronic renal disease via autophagy of vascular smooth muscle cells.iScience · 2023Article
- A Drug Repurposing Pipeline Based on Bladder Cancer Integrated Proteotranscriptomics Signatures.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Deep Learning-Assisted Repurposing of Plant Compounds for Treating Vascular Calcification: An In Silico Study with Experimental Validation.Oxidative medicine and cellular longevity · 2022Article
- Review
- SGLT2-Inhibition reverts urinary peptide changes associated with severe COVID-19: An in-silico proof-of-principle of proteomics-based drug repurposing.Proteomics · 2021Article
- Medial Arterial Calcification: JACC State-of-the-Art Review.Journal of the American College of Cardiology · 2021Review
- Evaluation of connectivity map shows limited reproducibility in drug repositioning.Scientific reports · 2021Article
- From organic and inorganic phosphates to valvular and vascular calcifications.Cardiovascular research · 2021Review
- Preexisting hypertension and pregnancy-induced hypertension reveal molecular differences in placental proteome in rodents.Physiological genomics · 2021Article
- Inflammation: a putative link between phosphate metabolism and cardiovascular disease.Clinical science (London, England : 1979) · 2021Review
- A Novel Pipeline for Drug Repurposing for Bladder Cancer Based on Patients' Omics Signatures.Cancers · 2020Article
- Review
- Connectivity mapping of glomerular proteins identifies dimethylaminoparthenolide as a new inhibitor of diabetic kidney disease.Scientific reports · 2020Article
- Molecular Changes in Tissue Proteome during Prostate Cancer Development: Proof-of-Principle Investigation.Diagnostics (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
23 authors at 10 institutions in 6 countries.
Funding
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.
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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 Socratic graph.