ArticleArteriosclerosis, thrombosis, and vascular biology2022
Preventing Cholesterol-Induced Perk (Protein Kinase RNA-Like Endoplasmic Reticulum Kinase) Signaling in Smooth Muscle Cells Blocks Atherosclerotic Plaque Formation.
Article in Arteriosclerosis, thrombosis, and vascular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06860295 (The Architectural Immunoregulation in Atherosclerotic Disease), which is not on this map. Cited by 21 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.
The Architectural Immunoregulation in Atherosclerotic Disease: A Single-Cell RNA Sequencing and Spatial Biology Approach
Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Energetic Decoding of VSMC Plasticity: Metabolic Reprogramming and Phenotypic Switching.Cardiovascular drugs and therapy · 2026Review
- Atherosclerotic Cell Fates: A Single-Cell View of ER Stress.Journal of cardiovascular development and disease · 2026Review
- FAPI PET/CT in post-PCI coronary disease: in-stent restenosis characterization, MACE association, and limited short-term modulation by lipid-lowering therapy: FAPI athero trial.European journal of nuclear medicine and molecular imaging · 2026Observational
- Etomidate Prevents Homocysteine‑Induced Endothelial Dysfunction by Suppressing PERK‑eIF2α‑ATF4 Signaling, Oxidative Stress, Mitochondrial Injury, and Autophagic Dysregulation.Journal of biochemical and molecular toxicology · 2026Article
- PERK Is Dispensable for Smooth Muscle Cell Phenotype Switching in Atherosclerosis.Arteriosclerosis, thrombosis, and vascular biology · 2026Article
- Article
- Immune checkpoint inhibitor-driven smooth muscle cell phenotypic modulation: a potential contributor to atherosclerotic risk associated with these therapies.Frontiers in cardiovascular medicine · 2026Article
- SMC Abca1 and Abcg1 Deficiency Enhances Urinary Bladder Distension but Not Atherosclerosis.Circulation research · 2025Article
- Inhibition of vascular smooth muscle cell PERK/ATF4 ER stress signaling protects against abdominal aortic aneurysms.JCI insight · 2025Article
- HRD1 reduction promotes cholesterol-induced vascular smooth muscle cell phenotypic change via endoplasmic reticulum stress.Molecular and cellular biochemistry · 2024Article
- TUDCA alleviates atherosclerosis by inhibiting AIM2 inflammasome and enhancing cholesterol efflux capacity in macrophage.iScience · 2024Article
- Protein-rich foods, sea foods, and gut microbiota amplify immune responses in chronic diseases and cancers - Targeting PERK as a novel therapeutic strategy for chronic inflammatory diseases, neurodegenerative disorders, and cancer.Pharmacology & therapeutics · 2024Review
- Activation of the PERK-CHOP signaling pathway during endoplasmic reticulum stress contributes to olanzapine-induced dyslipidemia.Acta pharmacologica Sinica · 2024Article
- The many roles of cathepsins in restenosis.Heliyon · 2024Article
- Emerging applications of single-cell profiling in precision medicine of atherosclerosis.Journal of translational medicine · 2024Review
- Re-analysis of single-cell transcriptomics reveals a critical role of macrophage-like smooth muscle cells in advanced atherosclerotic plaque.Theranostics · 2024Article
- The cGAS-STING/PERK-eIF2α: Individual or Potentially Collaborative Signaling Transduction in Cardiovascular Diseases.International journal of biological sciences · 2024Review
- Pericentrin deficiency in smooth muscle cells augments atherosclerosis through HSF1-driven cholesterol biosynthesis and PERK activation.JCI insight · 2023Article
- Smooth muscle α-actin missense variant promotes atherosclerosis through modulation of intracellular cholesterol in smooth muscle cells.European heart journal · 2023Article
- Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.Bioactive materials · 2023Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundVascular smooth muscle cells (SMCs) undergo complex phenotypic modulation with atherosclerotic plaque formation in hyperlipidemic mice, which is characterized by de-differentiation and heterogeneous increases in the expression of macrophage, fibroblast, osteogenic, and stem cell markers. An increase of cellular cholesterol in SMCs triggers similar phenotypic changes in vitro with exposure to free cholesterol due to cholesterol entering the endoplasmic reticulum, triggering endoplasmic reticulum stress and activating Perk (protein kinase RNA-like endoplasmic reticulum kinase) signaling.
methodsWe generated an SMC-specific
resultsSMC-specific deletion of Perk reduces atherosclerotic plaque formation in male hyperlipidemic mice by 80%. Single-cell transcriptomic data identify 2 clusters of modulated SMCs in hyperlipidemic mice, one of which is absent when
conclusionsOur results indicate that hypercholesterolemia drives both Perk-dependent and Perk-independent SMC modulation and that deficiency of Perk significantly blocks atherosclerotic plaque formation.
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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.