ArticleCirculation2014
Double-stranded RNA-dependent protein kinase deficiency protects the heart from systolic overload-induced congestive heart failure.
Article in Circulation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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.
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Who cites it
26 citing papers in PubMed, 46 citations in OpenAlex.
- Review
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- Reduced Expression of UPRmt Proteins HSP10, HSP60, HTRA2, OMA1, SPG7, and YME1L Is Associated with Accelerated Heart Failure in Humans.Biomedicines · 2025Article
- CD8 T cells promote heart failure progression in mice with preexisting left ventricular dysfunction.Frontiers in immunology · 2024Article
- FAM210A regulates mitochondrial translation and maintains cardiac mitochondrial homeostasis.Cardiovascular research · 2023Article
- Polynucleotide phosphorylase protects against renal tubular injury via blocking mt-dsRNA-PKR-eIF2α axis.Nature communications · 2023Article
- IL-12α deficiency attenuates pressure overload-induced cardiac inflammation, hypertrophy, dysfunction, and heart failure progression.Frontiers in immunology · 2023Article
- Article
- Formation of Double Stranded RNA Provokes Smooth Muscle Contractions and Structural Modifications in Bladder Ischemia.Research and reports in urology · 2022Article
- The Mitochondrial Unfolded Protein Response: A Novel Protective Pathway Targeting Cardiomyocytes.Oxidative medicine and cellular longevity · 2022Review
- Integrated Stress Response Couples Mitochondrial Protein Translation With Oxidative Stress Control.Circulation · 2021Article
- Translation Regulation by eIF2α Phosphorylation and mTORC1 Signaling Pathways in Non-Communicable Diseases (NCDs).International journal of molecular sciences · 2020Review
- Mitochondrial unfolded protein response, mitophagy and other mitochondrial quality control mechanisms in heart disease and aged heart.Croatian medical journal · 2020Review
- Effects of Oxidative Stress on Protein Translation: Implications for Cardiovascular Diseases.International journal of molecular sciences · 2020Review
- PERK-eIF2α-ATF4 signaling contributes to osteogenic differentiation of periodontal ligament stem cells.Journal of molecular histology · 2020Article
- Mechanical Regulation of Protein Translation in the Cardiovascular System.Frontiers in cell and developmental biology · 2020Review
- Profound Increase of Lung Airway Resistance in Heart Failure: a Potential Important Contributor for Dyspnea.Journal of cardiovascular translational research · 2019Article
- 2-aminopurine suppresses the TGF-β1-induced epithelial-mesenchymal transition and attenuates bleomycin-induced pulmonary fibrosis.Cell death discovery · 2018Article
- PKR: A Kinase to Remember.Frontiers in molecular neuroscience · 2018Review
- Role of bone marrow-derived CD11cBasic research in cardiology · 2017Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundDouble-stranded RNA-dependent protein kinase (PKR) is a eukaryotic initiation factor 2α kinase that inhibits mRNA translation under stress conditions. PKR also mediates inflammatory and apoptotic signaling independently of translational regulation. Congestive heart failure is associated with cardiomyocyte hypertrophy, inflammation, and apoptosis, but the role of PKR in left ventricular hypertrophy and the development of congestive heart failure has not been examined. METHODS AND
resultsWe observed increased myocardial PKR expression and translocation of PKR into the nucleus in humans and mice with congestive heart failure. To determine the impact of PKR on the development of congestive heart failure, PKR knockout and wild-type mice were exposed to pressure overload produced by transverse aortic constriction. Although heart size increased similarly in wild-type and PKR knockout mice after transverse aortic constriction, PKR knockout mice exhibited very little pulmonary congestion, well-preserved left ventricular ejection fraction and contractility, and significantly less myocardial fibrosis compared with wild-type mice. Bone marrow-derived cells from wild-type mice did not abolish the cardiac protective effect observed in PKR knockout mice, whereas bone marrow-derived cells from PKR knockout mice had no cardiac protective effect in wild-type mice. Mechanistically, PKR knockout attenuated transverse aortic constriction-induced tumor necrosis factor-α expression and leukocyte infiltration and lowered cardiac expression of proapoptotic factors (Bax and caspase-3), so that PKR knockout hearts were more resistant to transverse aortic constriction-induced cardiomyocyte apoptosis. PKR depletion in isolated cardiomyocytes also conferred protection against tumor necrosis factor-α- or lipopolysaccharide-induced apoptosis.
conclusionPKR is a maladaptive factor upregulated in hemodynamic overload that contributes to myocardial inflammation, cardiomyocyte apoptosis, and the development of congestive heart failure.
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Registered trials
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