ArticleJournal of the American Heart Association2013
PERK-eIF2α-ATF4-CHOP signaling contributes to TNFα-induced vascular calcification.
Article in Journal of the American Heart Association, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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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.
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Who cites it
70 citing papers in PubMed, 125 citations in OpenAlex.
- Review
- Adipose-Derived Proinflammatory Visfatin Promotes Vascular Calcification via TLR4 and is Suppressed by Empagliflozin.Inflammation · 2026Article
- Human biliary atresia extrahepatic cholangiocyte organoids express increased ER and oxidative stress, altered drug metabolism and cell polarity changes.Frontiers in bioengineering and biotechnology · 2026Article
- Comprehensive Review of Mechanisms and Translational Perspectives on Programmed Cell Death in Vascular Calcification.Biomolecules · 2025Review
- Inflammation, Apoptosis, and Fibrosis in Diabetic Nephropathy: Molecular Crosstalk in Proximal Tubular Epithelial Cells and Therapeutic Implications.Current issues in molecular biology · 2025Review
- Novel roles of Nrf3-Trim5 axis in vascular smooth muscle cell dysfunctions and neointimal hyperplasia.Cardiovascular research · 2025Article
- Deoxycholic Acid and Cognitive Impairment and Decline in the Chronic Renal Insufficiency Cohort (CRIC).Kidney medicine · 2025Article
- Altered protein homeostasis in cardiovascular diseases contributes to Alzheimer's-like neuropathology.Basic research in cardiology · 2025Article
- Inhibition of vascular smooth muscle cell PERK/ATF4 ER stress signaling protects against abdominal aortic aneurysms.JCI insight · 2025Article
- Activation of the IKK2/NF-κB pathway in VSMCs inhibits calcified vascular stiffness in CKD.JCI insight · 2024Article
- The pathogenesis and targeted therapies of intervertebral disc degeneration induced by cartilage endplate inflammation.Frontiers in cell and developmental biology · 2024Review
- Activation of PERK/eIF2α/ATF4/CHOP branch of endoplasmic reticulum stress response and cooperation between HIF-1α and ATF4 promotes Daprodustat-induced vascular calcification.Frontiers in pharmacology · 2024Article
- Exosomal miR-129 and miR-342 derived from intermittent hypoxia-stimulated vascular smooth muscle cells inhibit the eIF2α/ATF4 axis from preventing calcified aortic valvular disease.Journal of cell communication and signaling · 2023Article
- Antidepressants as Autophagy Modulators for Cancer Therapy.Molecules (Basel, Switzerland) · 2023Review
- Targeted PERK inhibition with biomimetic nanoclusters confers preventative and interventional benefits to elastase-induced abdominal aortic aneurysms.Bioactive materials · 2023Article
- Review
- Transcription factors: key regulatory targets of vascular smooth muscle cell in atherosclerosis.Molecular medicine (Cambridge, Mass.) · 2023Review
- Bile Acid Network and Vascular Calcification-Associated Diseases: Unraveling the Intricate Connections and Therapeutic Potential.Clinical interventions in aging · 2023Review
- Arterial Stiffness and the Canonical WNT/β-catenin Pathway.Current hypertension reports · 2022Review
- 25-hydroxyvitamin D-1α-hydroxylase (CYP27B1) induces ectopic calcification.Journal of clinical biochemistry and nutrition · 2022Article
10 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundVascular calcification is a common feature in patients with chronic kidney disease (CKD). CKD increases serum levels of tumor necrosis factor-α (TNFα), a critical mediator of vascular calcification. However, the molecular mechanism by which TNFα promotes CKD-dependent vascular calcification remains obscure. The purpose of the present study was to investigate whether TNFα-induced vascular calcification in CKD is caused by the endoplasmic reticulum response involving protein kinase RNA-like endoplasmic reticulum kinase (PERK), eukaryotic initiation factor 2α (eIF2α), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP). METHODS AND
resultsWe examined the effects of TNFα on the endoplasmic reticulum (ER) stress response of vascular smooth muscle cells (VSMCs). TNFα treatment drastically induced the PERK-eIF2α-ATF4-CHOP axis of the ER stress response in VSMCs. PERK, ATF4, and CHOP shRNA-mediated knockdowns drastically inhibited mineralization and osteogenesis of VSMCs induced by TNFα. CKD induced by 5/6 nephrectomies activated the PERK-eIF2α-ATF4-CHOP axis of the ER stress response in the aortas of ApoE-/- mice with increased aortic TNFα expression and vascular calcification. Treatment of 5/6 nephrectomized ApoE-/- mice with the TNFα neutralizing antibody or chemical Chaperones reduced aortic PERK-eIF2α-ATF4-CHOP signaling of the ER stress increased by CKD. This resulted in the inhibition of CKD-dependent vascular calcification.
conclusionsThese results suggest that TNFα induces the PERK-eIF2α-ATF4-CHOP axis of the ER stress response, leading to CKD-dependent vascular calcification.
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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.