ArticleProceedings of the National Academy of Sciences of the United States of America2017
Targeting IRE1 with small molecules counteracts progression of atherosclerosis.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
What it found
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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
117 citing papers in PubMed, 191 citations in OpenAlex.
- Atherosclerotic Cell Fates: A Single-Cell View of ER Stress.Journal of cardiovascular development and disease · 2026Review
- PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- IRE1-XBP1driven induction of TMED9 stabilizes ATF6 during ER stress to promote cell survival.Cellular & molecular biology letters · 2026Article
- Inositol Requiring Enzyme 1α Mediates Hypertension and Vascular Remodeling.Hypertension (Dallas, Tex. : 1979) · 2026Article
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- TRIB3 Links Endoplasmic Reticulum Stress to Impaired Efferocytosis in Atherosclerosis.Circulation research · 2025Article
- Short-chain fatty acid butyrate against TMAO activating endoplasmic-reticulum stress and PERK/IRE1-axis with reducing atrial arrhythmia.Journal of advanced research · 2025Article
- Article
- Homeostasis control in health and disease by the unfolded protein response.Nature reviews. Molecular cell biology · 2025Review
- The role of the ER stress sensor IRE1 in cardiovascular diseases.Molecular and cellular biochemistry · 2025Review
- Ire1 inhibitors attenuateFrontiers in microbiology · 2025Article
- Emerging role of IRE1α in vascular diseases.Journal of cell communication and signaling · 2024Review
- IRE1α pathway: A potential bone metabolism mediator.Cell proliferation · 2024Review
- Targeting chromosomal instability in patients with cancer.Nature reviews. Clinical oncology · 2024Review
- Endoplasmic Reticulum Membrane Homeostasis and the Unfolded Protein Response.Cold Spring Harbor perspectives in biology · 2024Review
- Article
- IRE1α determines ferroptosis sensitivity through regulation of glutathione synthesis.Nature communications · 2024Article
- Milestone Papers on Signal Transduction Mechanisms of Hypertension and Its Complications.Hypertension (Dallas, Tex. : 1979) · 2024Review
- IRE1α: from the function to the potential therapeutic target in atherosclerosis.Molecular and cellular biochemistry · 2024Review
- Two sides of the same coin: Non-alcoholic fatty liver disease and atherosclerosis.Vascular pharmacology · 2024Review
57 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Metaflammation, an atypical, metabolically induced, chronic low-grade inflammation, plays an important role in the development of obesity, diabetes, and atherosclerosis. An important primer for metaflammation is the persistent metabolic overloading of the endoplasmic reticulum (ER), leading to its functional impairment. Activation of the unfolded protein response (UPR), a homeostatic regulatory network that responds to ER stress, is a hallmark of all stages of atherosclerotic plaque formation. The most conserved ER-resident UPR regulator, the kinase/endoribonuclease inositol-requiring enzyme 1 (IRE1), is activated in lipid-laden macrophages that infiltrate the atherosclerotic lesions. Using RNA sequencing in macrophages, we discovered that IRE1 regulates the expression of many proatherogenic genes, including several important cytokines and chemokines. We show that IRE1 inhibitors uncouple lipid-induced ER stress from inflammasome activation in both mouse and human macrophages. In vivo, these IRE1 inhibitors led to a significant decrease in hyperlipidemia-induced IL-1β and IL-18 production, lowered T-helper type-1 immune responses, and reduced atherosclerotic plaque size without altering the plasma lipid profiles in apolipoprotein E-deficient mice. These results show that pharmacologic modulation of IRE1 counteracts metaflammation and alleviates atherosclerosis.
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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.