ArticleThe Journal of clinical investigation2011
Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease.
Article in The Journal of clinical investigation, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 255 papers, 2 of them syntheses 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.
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
255 citing papers in PubMed, 2 syntheses or guidelines pooled it, 527 citations in OpenAlex.
- Ancestry- and Age-Dependent Effects of NOS3 Polymorphisms on Coronary Heart Disease Risk: A Meta-analysis.Cardiovascular toxicology · 2025Pooled it
- eNOS rs2070744 polymorphism might influence predisposition to hemorrhagic cerebral vascular diseases in East Asians: A meta-analysis.Brain and behavior · 2020Pooled it
- Trial
- Impact of different training modalities on high-density lipoprotein function in HFpEF patients: a substudy of the OptimEx trial.ESC heart failure · 2022Trial
- HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.Disease markers · 2021Trial
- Effects of Endurance and Endurance-Strength Training on Endothelial Function in Women with Obesity: A Randomized Trial.International journal of environmental research and public health · 2019Trial
- Trial
- Effectiveness of a physical activity program on cardiovascular disease risk in adult primary health-care users: the "Pas-a-Pas" community intervention trial.BMC public health · 2017Trial
- Anti-inflammatory treatment improves high-density lipoprotein function in rheumatoid arthritis.Heart (British Cardiac Society) · 2017Trial
- Serum Concentration of HDL Particles Predicts Mortality in Acute Heart Failure Patients.Scientific reports · 2017Trial
- Effects of urban fine particulate matter and ozone on HDL functionality.Particle and fibre toxicology · 2016Trial
- Trial
- Unravelling the Therapeutic Potential of Cysteine for Cardiovascular Health.International journal of molecular sciences · 2026Review
- The Shared IL-12/IL-35 p35 Subunit Is Associated With Heightened Atherogenic Risk in African Patients With Type 2 Diabetes.Endocrinology, diabetes & metabolism · 2026Article
- High-density lipoprotein antioxidant function is associated with lipid profiles and lipid-lowering therapy.Science China. Life sciences · 2026Article
- Biology of HDL: From Structural Heterogeneity to Dysfunctional Remodeling in Cardiovascular Disease and Comorbidities.Antioxidants (Basel, Switzerland) · 2026Review
- Associations Between High-Density Lipoprotein Subfraction Profiles and Heart Rate Response Following Submaximal Exercise.Biology · 2026Article
- Review
- MicroRNA-155 at the crossroads of inflammation and vascular dysfunction in essential hypertension.Molecular biology reports · 2026Review
- The association of triglyceride-glucose index and uric acid-high-density lipoprotein cholesterol ratio with the risk of uterine fibroids: a real-world analysis based on health examination data.Journal of health, population, and nutrition · 2026Article
195 more citing papers are in PubMed but not listed here.
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Authors and funding
26 authors at 6 institutions in 4 countries.
Funding
Abstract
Therapies that raise levels of HDL, which is thought to exert atheroprotective effects via effects on endothelium, are being examined for the treatment or prevention of coronary artery disease (CAD). However, the endothelial effects of HDL are highly heterogeneous, and the impact of HDL of patients with CAD on the activation of endothelial eNOS and eNOS-dependent pathways is unknown. Here we have demonstrated that, in contrast to HDL from healthy subjects, HDL from patients with stable CAD or an acute coronary syndrome (HDLCAD) does not have endothelial antiinflammatory effects and does not stimulate endothelial repair because it fails to induce endothelial NO production. Mechanistically, this was because HDLCAD activated endothelial lectin-like oxidized LDL receptor 1 (LOX-1), triggering endothelial PKCβII activation, which in turn inhibited eNOS-activating pathways and eNOS-dependent NO production. We then identified reduced HDL-associated paraoxonase 1 (PON1) activity as one molecular mechanism leading to the generation of HDL with endothelial PKCβII-activating properties, at least in part due to increased formation of malondialdehyde in HDL. Taken together, our data indicate that in patients with CAD, HDL gains endothelial LOX-1- and thereby PKCβII-activating properties due to reduced HDL-associated PON1 activity, and that this leads to inhibition of eNOS-activation and the subsequent loss of the endothelial antiinflammatory and endothelial repair-stimulating effects of HDL.
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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.