Evidence map›Paper›PMID 36829979›Full record

ArticleAntioxidants (Basel, Switzerland)2023

Hypochlorous Acid and Chloramines Induce Specific Fragmentation and Cross-Linking of the G1-IGD-G2 Domains of Recombinant Human Aggrecan, and Inhibit ADAMTS1 Activity.

Yihe Wang, Astrid Hammer, Gerald Hoefler, Ernst Malle, Clare L Hawkins, Christine Y Chuang, Michael J Davies

Open access · goldAbstract read
In one paragraph

Article in Antioxidants (Basel, Switzerland), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.8field-weighted citation impact, top 26% 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

4 citing papers in PubMed, 5 citations in OpenAlex.

  1. Article
  2. Review
  3. Review
  4. Article
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

7 authors at 2 institutions in 2 countries.

Yihe WangDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0001-7167-3788
Astrid HammerDivision of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.
Gerald HoeflerInstitute of Pathology, Diagnostic & Research Center for Molecular BioMedicine, Medical University of Graz, 8010 Graz, Austria.ORCID 0000-0002-9056-3063
Ernst MalleDivision of Molecular Biology and Biochemistry, Gottfried Schatz Research Center, Medical University of Graz, 8010 Graz, Austria.
Clare L HawkinsDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0003-2738-5089
Christine Y ChuangDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0001-6144-632X
Michael J DaviesDepartment of Biomedical Sciences, Panum Institute, University of Copenhagen, 2200 Copenhagen, Denmark.ORCID 0000-0002-5196-6919
University of Copenhagen · DKMedical University of Graz · AT

Funding

China Scholarship Council 201909110076Novo Nordisk Foundation NNF13OC0004294Novo Nordisk Foundation NNF20SA0064214
6 · The paper itself

Abstract

Atherosclerosis is a chronic inflammatory disease and a leading cause of mortality. It is characterized by arterial wall plaques that contain high levels of cholesterol and other lipids and activated leukocytes covered by a fibrous cap of extracellular matrix (ECM). The ECM undergoes remodelling during atherogenesis, with increased expression of aggrecan, a proteoglycan that binds low-density-lipoproteins (LDL). Aggrecan levels are regulated by proteases, including a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1). Activated leukocytes release myeloperoxidase (MPO) extracellularly, where it binds to proteins and proteoglycans. Aggrecan may therefore mediate colocalization of MPO and LDL. MPO generates hypochlorous acid (HOCl) and chloramines (RNHCl species, from reaction of HOCl with amines on amino acids and proteins) that damage LDL and proteins, but effects on aggrecan have not been examined. The present study demonstrates that HOCl cleaves truncated (G1-IGD-G2) recombinant human aggrecan at specific sites within the IGD domain, with these being different from those induced by ADAMTS1 which also cleaves within this region. Irreversible protein cross-links are also formed dose-dependently. These effects are limited by the HOCl scavenger methionine. Chloramines including those formed on amino acids, proteins, and ECM materials induce similar damage. HOCl and taurine chloramines inactivate ADAMTS1 consistent with a switch from proteolytic to oxidative aggrecan fragmentation. Evidence is also presented for colocalization of aggrecan and HOCl-generated epitopes in advanced human atherosclerotic plaques. Overall, these data show that HOCl and chloramines can induce specific modifications on aggrecan, and that these effects are distinct from those of ADAMTS1.

Indexed as

ADAMTSaggrecanchloraminesextracellular matrixhypochlorous acidMPO-H2O2-Cl− systemmyeloperoxidaseprotein oxidation

Identifiers

PMID36829979
PMCPMC9952545
OpenAlexW4319754753

What OpenQuestion holds

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LicenceCC BY
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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.