ArticleArteriosclerosis, thrombosis, and vascular biology2014
Effects of native and myeloperoxidase-modified apolipoprotein a-I on reverse cholesterol transport and atherosclerosis in mice.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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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.
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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
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 146 citations in OpenAlex.
- Cholesterol Efflux Capacity and Its Association With Adverse Cardiovascular Events: A Systematic Review and Meta-Analysis.Frontiers in cardiovascular medicine · 2021Pooled it
- Oral Apolipoprotein A-I Mimetic D-4F Lowers HDL-Inflammatory Index in High-Risk Patients: A First-in-Human Multiple-Dose, Randomized Controlled Trial.Clinical and translational science · 2017Trial
- Trial
- Synthesis of Apolipoprotein A-I in Human Macrophages Enhances their Migratory Activity.Cell biochemistry and biophysics · 2026Article
- HDL Regulates TGFβ-Receptor Lipid Raft Partitioning, Restoring Contractile Features of Cholesterol-Loaded Vascular Smooth Muscle Cells.JACC. Basic to translational science · 2026Article
- Apolipoprotein A (ApoA) in Neurological Disorders: Connections and Insights.International journal of molecular sciences · 2025Review
- Myeloperoxidase as a Promising Therapeutic Target after Myocardial Infarction.Antioxidants (Basel, Switzerland) · 2024Review
- Biological basis and proposed mechanism of action of CSL112 (apolipoprotein A-I [human]) for prevention of major adverse cardiovascular events in patients with myocardial infarction.European heart journal. Cardiovascular pharmacotherapy · 2023Review
- HDL Function and Atherosclerosis: Reactive Dicarbonyls as Promising Targets of Therapy.Circulation research · 2023Review
- Candidate SNP Markers Significantly Altering the Affinity of TATA-Binding Protein for the Promoters of Human Hub Genes for Atherogenesis, Atherosclerosis and Atheroprotection.International journal of molecular sciences · 2023Article
- Hypochlorous Acid and Chloramines Induce Specific Fragmentation and Cross-Linking of the G1-IGD-G2 Domains of Recombinant Human Aggrecan, and Inhibit ADAMTS1 Activity.Antioxidants (Basel, Switzerland) · 2023Article
- Serum MPO levels and activities are associated with angiographic coronary atherosclerotic plaque progression in type 2 diabetic patients.BMC cardiovascular disorders · 2022Article
- Vulnerable Atherosclerotic Plaque: Is There a Molecular Signature?International journal of molecular sciences · 2022Review
- ApoA-I Infusion Therapies Following Acute Coronary Syndrome: Past, Present, and Future.Current atherosclerosis reports · 2022Review
- Antiatherosclerotic Effects of CSL112 Mediated by Enhanced Cholesterol Efflux Capacity.Journal of the American Heart Association · 2022Review
- HDL Is Not Dead Yet.Biomedicines · 2022Review
- HDL and ASCVD.Advances in experimental medicine and biology · 2022Article
- Article
- The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk.BMC cardiovascular disorders · 2021Observational
- Macrophages in Atherosclerosis, First or Second Row Players?Biomedicines · 2021Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 1 institution in 2 countries.
Funding
Abstract
objectivePreclinical and clinical studies have shown beneficial effects of infusions of apolipoprotein A-I (ApoA-I) on atherosclerosis. ApoA-I is also a target for myeloperoxidase-mediated oxidation, leading in vitro to a loss of its ability to promote ATP-binding cassette transporter A1-dependent macrophage cholesterol efflux. Therefore, we hypothesized that myeloperoxidase-mediated ApoA-I oxidation would impair its promotion of reverse cholesterol transport in vivo and the beneficial effects on atherosclerotic plaques. APPROACH AND
resultsApoA-I(-/-) or apolipoprotein E-deficient mice were subcutaneously injected with native human ApoA-I, oxidized human ApoA-I (myeloperoxidase/hydrogen peroxide/chloride treated), or carrier. Although early postinjection (8 hours) levels of total ApoA-I in plasma were similar for native versus oxidized human ApoA-I, native ApoA-I primarily resided within the high-density lipoprotein fraction, whereas the majority of oxidized human ApoA-I was highly cross-linked and not high-density lipoprotein particle associated, consistent with impaired ATP-binding cassette transporter A1 interaction. In ApoA-I(-/-) mice, ApoA-I oxidation significantly impaired reverse cholesterol transport in vivo. In advanced aortic root atherosclerotic plaques of apolipoprotein E-deficient mice, native ApoA-I injections led to significant decreases in lipid content, macrophage number, and an increase in collagen content; in contrast, oxidized human ApoA-I failed to mediate these changes. The decrease in plaque macrophages with native ApoA-I was accompanied by significant induction of their chemokine receptor CCR7. Furthermore, only native ApoA-I injections led to a significant reduction of inflammatory M1 and increase in anti-inflammatory M2 macrophage markers in the plaques.
conclusionsMyeloperoxidase-mediated oxidation renders ApoA-I dysfunctional and unable to (1) promote reverse cholesterol transport, (2) mediate beneficial changes in the composition of atherosclerotic plaques, and (3) pacify the inflammatory status of plaque macrophages.
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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.