ArticleThe Journal of clinical investigation2013
Myeloperoxidase, paraoxonase-1, and HDL form a functional ternary complex.
Article in The Journal of clinical investigation, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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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
147 citing papers in PubMed, 269 citations in OpenAlex.
- Effect of Atorvastatin Combined With Herb-Partitioned Moxibustion on PON-1 in Patients With Atherosclerotic Cerebral Infarction: A Randomized Controlled Trial.Brain and behavior · 2026Trial
- Effect of yerba mate and green tea on paraoxonase and leptin levels in patients affected by overweight or obesity and dyslipidemia: a randomized clinical trial.Nutrition journal · 2019Trial
- Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis.Heart (British Cardiac Society) · 2017Trial
- Effect of two lipid-lowering strategies on high-density lipoprotein function and some HDL-related proteins: a randomized clinical trial.Lipids in health and disease · 2017Trial
- Improvement of High-Density Lipoprotein Function in Patients With Early Rheumatoid Arthritis Treated With Methotrexate Monotherapy or Combination Therapies in a Randomized Controlled Trial.Arthritis & rheumatology (Hoboken, N.J.) · 2017Trial
- The therapeutic efficacy of intensive medical therapy in ameliorating high-density lipoprotein dysfunction in subjects with type two diabetes.Lipids in health and disease · 2016Trial
- High-density lipoprotein antioxidant function is associated with lipid profiles and lipid-lowering therapy.Science China. Life sciences · 2026Article
- Reduced Serum PON1 Lactonase Activity Is Associated with Mild Cognitive Impairment and Mixed Dementia.Antioxidants (Basel, Switzerland) · 2026Article
- The Effect of Iatrogenic Hypothyroidism on Lipoprotein Subfractions and Markers of HDL Function in Patients with Differentiated Thyroid Carcinoma.Life (Basel, Switzerland) · 2026Article
- Diagnostic and pathophysiological significance of serum myeloperoxidase, ischemia-modified albumin, paraoxonase-1 and galectin-3 in COVID-19 - parallels with myocarditis.BMC cardiovascular disorders · 2026Article
- Reduced antioxidant high-density lipoprotein function in heart failure with preserved ejection fraction.Clinical research in cardiology : official journal of the German Cardiac Society · 2026Observational
- Tetranectin and Paraoxonase-1 as Markers of Heart Failure.Medicina (Kaunas, Lithuania) · 2026Review
- Homocysteine thiolactone affects paraoxonase 1 activity via altered paraoxonase 1 distribution on high-density lipoprotein particles.Bioscience reports · 2026Article
- Myeloperoxidase (MPO) Enzymatic Activity, but Not Its Protein Concentration, Is Associated with the Risk of Type 2 Diabetes in Females, Regardless of Obesity Status.Antioxidants (Basel, Switzerland) · 2026Article
- Noncatalytic Functions Are Required for MPO and PON1 in Modulating the Involvement of Monocytes and Endothelial Cells in Atherosclerosis.Biochemistry research international · 2026Article
- HDL metabolism and function in diabetes mellitus.Nature reviews. Endocrinology · 2026Review
- Usefulness of plasma and apolipoprotein B-depleted serum samples in paraoxonase 1 assessment.Biochemistry and biophysics reports · 2025Article
- Oxidized high-density lipoprotein associates with cardiometabolic dysfunction in coronary artery disease and acute coronary syndrome.Journal of internal medicine · 2025Article
- Sex- and Ethnic-Specific Associations of Serum Lipids with Risk of 12 Cancers: Findings from 506,381 Adults in Two Large Cohorts.Antioxidants (Basel, Switzerland) · 2025Article
- High-density lipoproteins. Part 2. Impact of disease states on functionality.American journal of preventive cardiology · 2025Article
87 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 6 institutions in 3 countries.
Funding
Abstract
Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein-associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for HDL binding and PON1 function. Acute inflammation model studies with transgenic and knockout mice for either PON1 or MPO confirmed that MPO and PON1 reciprocally modulate each other's function in vivo. Further structure and function studies identified critical contact sites between APOA1 within HDL, PON1, and MPO, and proteomics studies of HDL recovered from acute coronary syndrome (ACS) subjects revealed enhanced chlorotyrosine content, site-specific PON1 methionine oxidation, and reduced PON1 activity. HDL thus serves as a scaffold upon which MPO and PON1 interact during inflammation, whereupon PON1 binding partially inhibits MPO activity, and MPO promotes site-specific oxidative modification and impairment of PON1 and APOA1 function.
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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 OpenQuestion graph.