ArticleCell cycle (Georgetown, Tex.)2012
Suppression of ERR targets by a PPARα/Sirt1 complex in the failing heart.
Article in Cell cycle (Georgetown, Tex.), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Fenofibrate as an Adjunct Therapy for Ulcerative Colitis: Targeting Inflammation via SIRT1, NLRP3, and AMPK Pathways: A Randomized Controlled Pilot Study.Drug design, development and therapy · 2024Trial
- Review
- Liver Metabolism at the Crossroads: The Reciprocal Control of Nutrient-Sensing Nuclear Receptors and Autophagy.International journal of molecular sciences · 2025Review
- The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK.Journal of pharmaceutical analysis · 2024Review
- Review article: vascular effects of PPARs in the context of NASH.Alimentary pharmacology & therapeutics · 2022Review
- SIRT1 haplo-insufficiency results in reduced cortical bone thickness, increased porosity and decreased estrogen receptor alpha in bone in adult 129/Sv female mice.Frontiers in endocrinology · 2022Article
- Mechanistic insights into the peroxisome proliferator-activated receptor alpha as a transcriptional suppressor.Frontiers in medicine · 2022Review
- Article
- The emerging role of estrogen related receptorα in complications of non-small cell lung cancers.Oncology letters · 2021Review
- Peroxisome Proliferator-Activated Receptors as Molecular Links between Caloric Restriction and Circadian Rhythm.Nutrients · 2020Review
- Review
- Trimetazidine in Heart Failure.Frontiers in pharmacology · 2020Review
- SIRT6 Promotes Hepatic Beta-Oxidation via Activation of PPARα.Cell reports · 2019Article
- Inducible Cardiac-Specific Deletion of Sirt1 in Male Mice Reveals Progressive Cardiac Dysfunction and Sensitization of the Heart to Pressure Overload.International journal of molecular sciences · 2019Article
- SIRT3 Blocks Aging-Associated Tissue Fibrosis in Mice by Deacetylating and Activating Glycogen Synthase Kinase 3β.Molecular and cellular biology · 2015Article
- Sirtuins in epigenetic regulation.Chemical reviews · 2015Review
- PPARs: Protectors or Opponents of Myocardial Function?PPAR research · 2015Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Heart failure is a leading cause of death worldwide. Estrogen-related receptors (ERRs) are a nuclear receptor subfamily that facilitates the transcription of contractile and nucleus-encoded mitochondrial genes in the heart. Impaired expression of these ERR target genes is frequently observed in human heart failure patients. However, the responsible molecular mechanism is not well-understood. Recently, we have shown that PPARα forms a protein complex with Sirt1, which is involved in the downregulation of ERR targets through direct interaction with the ERR response element (ERRE) in the failing heart. Here, we provide additional lines of evidence supporting the pathological involvement of the PPARα/Sirt1 complex in heart failure. Pressure overload-induced left ventricular (LV) hypertrophy was attenuated in mice with heterozygous knockout of either PPARα (PPARα (+/-) ) or Sirt1 (Sirt1 (+/-) ), whereas cardiac-specific PPARα and Sirt1 bigenic mice showed LV hypertrophy accompanied by a high mortality rate even without pressure overload. Microarray analyses indicated that nuclear-encoded mitochondrial genes were largely downregulated and mitochondrial morphological abnormalities were observed in PPARα/Sirt1 bigenic mice. Those downregulated mitochondrial genes frequently harbor the ERRE in the promoter regions. Artificial and physiological PPARα ligands suppressed reporter genes driven by the ERREs. PPARα bound to and recruited Sirt1 to the genomic flanking region of the ERREs in the heart. Pressure overload downregulated many ERR targets, which were partly normalized by PPARα (+/-) and Sirt1 (+/-) mice. These results suggest that PPARα and Sirt1 downregulate ERR target gene expression through direct interaction with the ERRE in the failing heart.
Indexed as
Identifiers
What OpenQuestion holds
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.