ArticleArteriosclerosis, thrombosis, and vascular biology2024
Diacylglycerols and Lysophosphatidic Acid, Enriched on Lipoprotein(a), Contribute to Monocyte Inflammation.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 1 of them a synthesis that pooled it.
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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
37 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Oxidized Phospholipids and Calcific Aortic Valvular Disease.Journal of the American College of Cardiology · 2024Pooled it
- Lipoprotein(a) lipidome and diet: responses to reducing saturated fat intake in African Americans in a randomized trial.Journal of lipid research · 2026Trial
- Lipoprotein(a) Lipidome: Responses to Reduced Dietary Saturated Fat Intake in Two Randomized Controlled Feeding Trials.Nutrients · 2025Trial
- Association of Elevated Lipoprotein(a) levels with vulnerable plaque features assessed by multimodality coronary imaging in patients with coronary artery disease: A systematic review and Meta-analysis.International journal of cardiology. Heart & vasculature · 2026Review
- The Roles of Lipoprotein(a) in Atherosclerosis - Minding the Knowledge Gaps.Current atherosclerosis reports · 2026Review
- Lipoprotein(a) Particle Core Remodeling and Apolipoprotein C-III Inhibition: Unraveling the Complexity of Lp(a) Metabolism in Hypertriglyceridemia.JACC. Basic to translational science · 2026Article
- LPA₃ signaling and biological functions: from physiological regulation to disease-targeted therapy.Molecular biology reports · 2026Review
- Associations of Elevated Lipoprotein(a) with C-Reactive Protein and Type 2 Diabetes in a Multiethnic Population.Biomedicines · 2026Article
- Anti-inflammatory agents in atherosclerosis-and a need for reform: Extraordinary claims require extraordinary evidence.Journal of internal medicine · 2026Article
- Role of Lipoprotein(a) in Aortic Valve Calcification: Inflammatory and Oxidative Mechanisms Involved.International journal of molecular sciences · 2026Review
- Comparative Proteomic Analysis of Lipoprotein(a): Method-Dependent Profiles and Disease Pathways.Journal of clinical medicine · 2026Article
- A novel immune-isolation method for direct quantification of triglycerides associated with lipoprotein(a).Journal of lipid research · 2026Article
- Lipoprotein(a) and Cardiovascular Disease: From Genetic Risk Factor to Therapeutic Target.Cells · 2026Review
- Progress in the Cross-Organ Biomarker oxLDL in Promoting Pathological Neovascular Diseases.Antioxidants (Basel, Switzerland) · 2026Review
- Thymic stromal lymphopoietin promotes abdominal aortic aneurysm formation by regulating macrophage polarization.Frontiers in immunology · 2026Article
- Temporal gut microbiota dysbiosis links metabolic impairment, LDL desialylation, and accelerated atherosclerosis in LDLRFrontiers in medicine · 2026Article
- A single-cell and spatial atlas of plaque macrophage states in human atherosclerosis.Frontiers in immunology · 2026Review
- Lipoprotein(a) and the Vascular Redox Interface: Linking Arteriosclerosis, Thrombosis, and Vascular Biology.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Lysophosphatidylcholine and lysophosphatidic acid as key messengers in atherosclerosis: from a lipid-inflammation vicious cycle to therapeutic translation.Frontiers in cardiovascular medicine · 2026Review
- Article
Corrections and comments
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Authors and funding
19 authors at 7 institutions in 4 countries.
Funding
Abstract
backgroundOxidized phospholipids play a key role in the atherogenic potential of lipoprotein(a) (Lp[a]); however, Lp(a) is a complex particle that warrants research into additional proinflammatory mediators. We hypothesized that additional Lp(a)-associated lipids contribute to the atherogenicity of Lp(a).
methodsUntargeted lipidomics was performed on plasma and isolated lipoprotein fractions. The atherogenicity of the observed Lp(a)-associated lipids was tested ex vivo in primary human monocytes by RNA sequencing, ELISA, Western blot, and transendothelial migratory assays. Using immunofluorescence staining and single-cell RNA sequencing, the phenotype of macrophages was investigated in human atherosclerotic lesions.
resultsCompared with healthy individuals with low/normal Lp(a) levels (median, 7 mg/dL [18 nmol/L]; n=13), individuals with elevated Lp(a) levels (median, 87 mg/dL [218 nmol/L]; n=12) demonstrated an increase in lipid species, particularly diacylglycerols (DGs) and lysophosphatidic acid (LPA). DG and the LPA precursor lysophosphatidylcholine were enriched in the Lp(a) fraction. Ex vivo stimulation with DG(40:6) demonstrated a significant upregulation in proinflammatory pathways related to leukocyte migration, chemotaxis, NF-κB (nuclear factor kappa B) signaling, and cytokine production. Functional assessment showed a dose-dependent increase in the secretion of IL (interleukin)-6, IL-8, and IL-1β after DG(40:6) and DG(38:4) stimulation, which was, in part, mediated via the NLRP3 (NOD [nucleotide-binding oligomerization domain]-like receptor family pyrin domain containing 3) inflammasome. Conversely, LPA-stimulated monocytes did not exhibit an inflammatory phenotype. Furthermore, activation of monocytes by DGs and LPA increased their transendothelial migratory capacity. Human atherosclerotic plaques from patients with high Lp(a) levels demonstrated colocalization of Lp(a) with M1 macrophages, and an enrichment of CD68
conclusionsLp(a)-associated DGs and LPA have a potential role in Lp(a)-induced monocyte inflammation by increasing cytokine secretion and monocyte transendothelial migration. This DG-induced inflammation is, in part, NLRP3 inflammasome dependent.
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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.