ArticleiScience2020
PERK-Mediated Suppression of microRNAs by Sildenafil Improves Mitochondrial Dysfunction in Heart Failure.
Article in iScience, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.
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
8 citing papers in PubMed, 1 synthesis or guideline pooled it, 12 citations in OpenAlex.
- Crosstalk between microRNA and Oxidative Stress in Heart Failure: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Cone photoreceptor phosphodiesterase PDE6H inhibition regulates cancer cell growth and metabolism, replicating the dark retina response.Cancer & metabolism · 2024Article
- LncRNAs and CircRNAs in Endoplasmic Reticulum Stress: A Promising Target for Cardiovascular Disease?International journal of molecular sciences · 2023Review
- miR-181c targets Parkin and SMAD7 in human cardiac fibroblasts: Validation of differential microRNA expression in patients with diabetes and heart failure with preserved ejection fraction.Mechanisms of ageing and development · 2023Article
- Neuron-specific translational control shift ensures proteostatic resilience during ER stress.The EMBO journal · 2022Article
- Inhibition of cardiac PERK signaling promotes peripartum cardiac dysfunction.Scientific reports · 2021Article
- Endoplasmic reticulum stress and unfolded protein response in cardiovascular diseases.Nature reviews. Cardiology · 2021Review
- Endoplasmic Reticulum Stress and miRNA Impairment in Aging and Age-Related Diseases.Frontiers in aging · 2021Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oxidative/nitrosative stress is a major trigger of cardiac dysfunction, involving the unfolded protein response and mitochondrial dysfunction. Activation of nitric oxide-cyclic guanosine monophosphate-protein kinase G signaling by sildenafil improves cardiac mal-remodeling during pressure-overload-induced heart failure. Transcriptome analysis was conducted in failing hearts with or without sildenafil treatment. Protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) downstream signaling pathways, EIF2 and NRF2, were significantly altered. Although EIF2 signaling was suppressed, NRF2 signaling was upregulated, inhibiting the maturation of miR 24-3p through EGFR-mediated Ago2 phosphorylation. To study the effect of sildenafil on these pathways, we generated cardiac-specific PERK knockout mice. In these mice, sildenafil could not inhibit the maturations, the nuclear translocation of NRF2 was suppressed, and mitochondrial dysfunction advanced. Altogether, these results show that PERK-mediated suppression of miRNAs by sildenafil is vital for maintaining mitochondrial homeostasis through NRF2-mediated oxidative stress response.
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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.