ArticleScience advances2016
Targeting macrophage necroptosis for therapeutic and diagnostic interventions in atherosclerosis.
Article in Science advances, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 179 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
179 citing papers in PubMed, 1 synthesis or guideline pooled it, 284 citations in OpenAlex.
- Macrophage-associated kinase signaling in atherosclerosis - a systematic review.Cell communication and signaling : CCS · 2026Pooled it
- A phase I randomized, double-blinded, placebo-controlled study assessing the safety and pharmacokinetics of RIPK1 inhibitor GFH312 in healthy subjects.Clinical and translational science · 2023Trial
- Cell death in ischemia-reperfusion injury: beyond a single-cell-death perspective.Biomarker research · 2026Review
- Deficiency of protein kinase Cδ reprograms macrophage immunometabolism to suppress pyroptosis and stabilize atherosclerotic plaques.Experimental & molecular medicine · 2026Article
- Macrophage extracellular traps accelerate atherosclerosis progression via Rap1 pathway-mediated necroptosis and phenotypic switching in vascular smooth muscle cells.Journal of translational medicine · 2026Article
- Adipocyte caspase-8 but not RIPK3 promotes adiposity.Cell death discovery · 2026Article
- Hyperlipidemia induces hippocampal inflammation and loss of vascularity and can be rescued by silencing RIPK1.Scientific reports · 2026Article
- Programmed Cell Death of Endothelial Cells in Ischemic Heart Disease: Mechanism and Potential Cell and Gene Therapeutic Prospects.Bioengineering (Basel, Switzerland) · 2026Review
- Current Insights into the Molecular Mechanisms of Intracranial Atherosclerosis and Their Therapeutic Implications.International journal of molecular sciences · 2026Review
- Distinct types of regulated cell death in atherosclerosis.Journal of pharmaceutical analysis · 2026Review
- Macrophage-derived galectin-3 contributes to pyroptosis, apoptosis and necroptosis through TLR4/MyD88/NF-κB/NLRP3 during atherosclerosis.Clinical and translational medicine · 2026Article
- Targeting MLKL-Driven Necroptosis: A Therapeutic Target in Inflammation and Host Defense.Biomolecules · 2026Review
- Targeting PANoptosis in atherosclerosis: bridging cell death mechanisms and therapy.Apoptosis : an international journal on programmed cell death · 2026Review
- Resveratrol Mediates Anti-Atherogenic Actions In Vitro and in LDL Receptor-Deficient Mice Fed a High-Fat Diet via Antioxidant, Anti-Inflammatory and Plaque-Stabilising Activities.Antioxidants (Basel, Switzerland) · 2026Article
- Research progress on targeted regulatory proteins in the prevention and treatment of atherosclerosis.Frontiers in immunology · 2026Review
- PANoptosis links gut dysbiosis to obstructive sleep apnea-associated atherosclerosis: a gut-vascular inflammatory axis.Frontiers in immunology · 2026Review
- Traditional Chinese Medicine Treatment for Coronary Heart Disease: Pathological Mechanisms of Modulating Cell Death Pathways.Journal of inflammation research · 2026Review
- Decoding the crosstalk: interplay between macrophage programmed cell death networks and cholesterol efflux.Frontiers in cardiovascular medicine · 2026Review
- Nanoengineered GATA3International journal of nanomedicine · 2026Article
- Microglial Necroptosis Mediated by RIPK3 Leads to Retinal Ganglion Cell Apoptosis Through the Release of FGF2 After Ischemia/Reperfusion.Journal of molecular neuroscience : MN · 2025Article
119 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
17 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atherosclerosis results from maladaptive inflammation driven primarily by macrophages, whose recruitment and proliferation drive plaque progression. In advanced plaques, macrophage death contributes centrally to the formation of plaque necrosis, which underlies the instability that promotes plaque rupture and myocardial infarction. Hence, targeting macrophage cell death pathways may offer promise for the stabilization of vulnerable plaques. Necroptosis is a recently discovered pathway of programmed cell necrosis regulated by RIP3 and MLKL kinases that, in contrast to apoptosis, induces a proinflammatory state. We show herein that necroptotic cell death is activated in human advanced atherosclerotic plaques and can be targeted in experimental atherosclerosis for both therapeutic and diagnostic interventions. In humans with unstable carotid atherosclerosis, expression of RIP3 and MLKL is increased, and MLKL phosphorylation, a key step in the commitment to necroptosis, is detected in advanced atheromas. Investigation of the molecular mechanisms underlying necroptosis showed that atherogenic forms of low-density lipoprotein increase RIP3 and MLKL transcription and phosphorylation-two critical steps in the execution of necroptosis. Using a radiotracer developed with the necroptosis inhibitor necrostatin-1 (Nec-1), we show that (123)I-Nec-1 localizes specifically to atherosclerotic plaques in Apoe (-/-) mice, and its uptake is tightly correlated to lesion areas by ex vivo nuclear imaging. Furthermore, treatment of Apoe (-/-) mice with established atherosclerosis with Nec-1 reduced lesion size and markers of plaque instability, including necrotic core formation. Collectively, our findings offer molecular insight into the mechanisms of macrophage cell death that drive necrotic core formation in atherosclerosis and suggest that this pathway can be used as both a diagnostic and therapeutic tool for the treatment of unstable atherosclerosis.
Indexed as
Identifiers
What OpenQuestion holds
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.