---
title: "N‑aldehyde–modified phosphatidylethanolamines (NAMPs) from lipid peroxidation inhibit efferocytosis"
id: "biorxiv-17-n-aldehyde-modified-phosphatidylethanolamines-formed-by-lipid-peroxidation"
canonical_url: "https://medichelpline.com/clinical-feed/biorxiv-17-n-aldehyde-modified-phosphatidylethanolamines-formed-by-lipid-peroxidation"
content_type: "clinical_feed_article"
specialty: "Cardiology"
source_name: "bioRxiv (Biomedical Preprints)"
source_url: "https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1?rss=1"
published_at: "2026-09-16T12:00:00.000Z"
evidence_level: "Verified Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# N‑aldehyde–modified phosphatidylethanolamines (NAMPs) from lipid peroxidation inhibit efferocytosis
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/biorxiv-17-n-aldehyde-modified-phosphatidylethanolamines-formed-by-lipid-peroxidation
- **Specialty:** [Cardiology](https://medichelpline.com/clinical-feed/cardiology.md)
- **Primary Source:** bioRxiv (Biomedical Preprints)
- **Source URL:** [Original Journal Publication](https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1?rss=1)
- **Published At:** 2026-09-16T12:00:00.000Z
- **Evidence Rating:** Verified Feed
## Executive GIST (TL;DR)
- The study examined whether reactive lipid aldehydes generated by **lipid peroxidation** form N‑aldehyde–modified phosphatidylethanolamines (**NAMPs**) and whether these species impair **efferocytosis**, the macrophage clearance of apoptotic cells. - Synthetic representative NAMP species tested included **N‑IsoLG‑PE**, **N‑HNE‑PE**, and **N‑Aze‑PE**; each inhibited efferocytosis in a concentration‑dependent manner. - Live‑cell real‑time efferocytosis assays used the Incucyte system to monitor ingestion of CypHer‑labeled apoptotic cells by bone marrow–derived macrophages. - Formation and levels of NAMPs under oxidative conditions were measured by liquid chromatography–mass spectrometry (LC–MS). - Hydrolysis of NAMPs with recombinant NAPE‑PLD abolished their inhibitory effect on efferocytosis; conversely, genetic deletion of macrophage NAPE‑PLD increased NAMP‑mediated inhibition. - Inhibition of glutathione peroxidase 4 (**GPX4**), an inhibitor of lipid peroxidation, raised macrophage NAMP concentrations and impaired efferocytosis. - Unmodified **HDL** enhanced efferocytosis, but HDL exposed to reactive lipid aldehydes or peroxidation accumulated NAMPs and then inhibited efferocytosis. - HDL isolated from people with familial hypercholesterolemia contained elevated levels of multiple NAMP species. - NAMPs also impaired macrophage cholesterol efflux, a process required to sustain continued efferocytosis. - Overall, the data indicate that NAMPs accumulate under conditions associated with lipid peroxidation and can directly reduce macrophage clearance of apoptotic cells, a mechanism relevant to chronic inflammation and atherosclerotic plaque necrosis.
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Reza Fadaei, [ View ORCID Profile](http://orcid.org/0009-0005-7511-7240)Annie C. Bernstein, Elizabeth A. Wayman, Azuah L. Gonzalez, Keri A. Tallman, Zahra Mashhadi, Abdul-musawwir Alli-oluwafuyi, [ View ORCID Profile](http://orcid.org/0000-0003-2976-6184)Sergey I. Dikalov, [ View ORCID Profile](http://orcid.org/0000-0002-9277-0453)MacRae F Linton, [ View ORCID Profile](http://orcid.org/0000-0001-5643-3102)Kasey C. Vickers, [ View ORCID Profile](http://orcid.org/0000-0002-1576-6274)Amanda C. Doran, [ View ORCID Profile](http://orcid.org/0000-0001-9879-8062)Sean S. Davies doi: https://doi.org/10.64898/2026.09.10.750792 This article is a preprint and has not been certified by peer review [[what does this mean?](https://www.biorxiv.org/about/FAQ#unrefereed)]. Reza Fadaei 1 Vanderbilt University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Reza%2BFadaei%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Fadaei%20R&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AReza%2BFadaei%2B) Annie C. Bernstein 1 Vanderbilt University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Annie%2BC.%2BBernstein%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Bernstein%20AC&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3AAnnie%2BC.%2BBernstein%2B) * [ORCID record for Annie C. 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Davies 1 Vanderbilt University; * [Find this author on Google Scholar](https://www.biorxiv.org/lookup/google-scholar?link_type=googlescholar&gs_type=author&author%5B0%5D=Sean%2BS.%2BDavies%2B "Open in new tab") * [Find this author on PubMed](https://www.biorxiv.org/lookup/external-ref?access_num=Davies%20SS&link_type=AUTHORSEARCH "Open in new tab") * [Search for this author on this site](https://www.biorxiv.org/search/author1%3ASean%2BS.%2BDavies%2B) * [ORCID record for Sean S. Davies](http://orcid.org/0000-0001-9879-8062 "Open in new tab") * For correspondence: sean.davies@vanderbilt.edu * [Abstract](https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_art/node:5784591/1) * [Info/History](https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1.article-info)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_info/node:5784591/1) * [Metrics](https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1.article-metrics)[](https://www.biorxiv.org/panels_ajax_tab/article_tab_metrics/node:5784591/1) * [ Preview PDF](https://www.biorxiv.org/content/10.64898/2026.09.10.750792v1.full.pdf+html)[](https://www.biorxiv.org/panels_ajax_tab/biorxiv_tab_pdf/node:5784591/1) ![Loading](https://www.biorxiv.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif) ## Abstract Objective: Impairments in efferocytosis, the phagocytic clearance of apoptotic cells, contribute to the development of chronic inflammation and promote the formation of large necrotic cores within atherosclerotic plaques. A better understanding of the factors that impair efferocytosis could lead to improved interventions. Many chronic inflammatory conditions feature excessive lipid peroxidation, which generates reactive lipid aldehydes that can potentially form N-aldehyde-modified phosphatidylethanolamines (NAMPs). We therefore investigated the extent to which levels of NAMPs are elevated under conditions of oxidative stress and whether exposure of macrophages to NAMPs inhibit efferocytosis. Approach and Results: The effects of synthetic NAMPs and lipid peroxidation on efferocytosis were measured using the Incucyte Live-Cell Analysis System to monitor rate of ingestion of CypHer-labeled apoptotic cells by cultured bone marrow-derived macrophages in real time. The extent of NAMP formation under various conditions was examined using liquid chromatography coupled with mass spectrometry. Several representative species of NAMPs (N-isolevuglandin-phosphatidylethanolamine, N-IsoLG-PE; N-4-hydroxynonenal-phosphatidylethanolamine, N-HNE-PE; and N-azeloyl-phosphatidylethanolamine, N-Aze-PE) inhibited efferocytosis in a concentration-dependent manner. Hydrolysis of NAMPs by recombinant N-acyl phosphatidylethanolamine hydrolyzing phospholipase D (NAPE-PLD) abolished their inhibitory activity, whereas genetic deletion of macrophage NAPE-PLD enhanced NAMP-mediated inhibition of efferocytosis. Blocking the inhibitor of lipid peroxidation, glutathione peroxidase 4 (GPX4), increased macrophage NAMP concentrations and impaired efferocytosis. Unmodified high-density lipoprotein (HDL) promoted efferocytosis, but exposing HDL to reactive lipid aldehydes or peroxidizing agents markedly increased NAMPs and this modified HDL inhibited efferocytosis. HDL isolated from subjects with familial hypercholesterolemia had elevated levels of multiple NAMP species. NAMPs impaired macrophage cholesterol efflux, which is required for continual efferocytosis. Conclusion: NAMPs accumulate under conditions associated with lipid peroxidation and inhibit the ability of macrophages to carry out efferocytosis. ### Competing Interest Statement The authors have declared no competing interest. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a [CC-BY-NC 4.0 International license](http://creativecommons.org/licenses/by-nc/4.0/). bioRxiv and medRxiv thank the following for their generous financial support: > The Chan Zuckerberg Initiative, Cold Spring Harbor Laboratory, the Sergey Brin Family Foundation, California Institute of Technology, Centre National de la Recherche Scientifique, Fred Hutchinson Cancer Center, Imperial College London, Massachusetts Institute of Technology, Stanford University, The University of Edinburgh, University of Washington, and Vrije Universiteit Amsterdam. [Donate to openRxiv ](https://www.zeffy.com/en-US/donation-form/donate-to-make-a-difference-10981) [ Back to top](https
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