ArticleCell death & disease2015
A novel miR-371a-5p-mediated pathway, leading to BAG3 upregulation in cardiomyocytes in response to epinephrine, is lost in Takotsubo cardiomyopathy.
Article in Cell death & disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.
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Who cites it
30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 54 citations in OpenAlex.
- MicroRNAs in Takotsubo Syndrome: A Systematic Review of Regulatory Networks in Stress-Induced Cardiomyopathy.International journal of molecular sciences · 2025Pooled it
- Genetic and Epigenetic Factors of Takotsubo Syndrome: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- A Genome-Wide Association Study of Takotsubo Syndrome.JACC. Basic to translational science · 2026Article
- The Genetic Puzzle of the Stress-Induced Cardiomyopathy (Takotsubo Syndrome): State of Art and Future Perspectives.Biomolecules · 2025Review
- MicroRNA Profiling in Chronic Limb-Threatening Ischemia Their Role in Arteriogenesis.The International journal of angiology : official publication of the International College of Angiology, Inc · 2025Article
- BAG3 in human tumors.Frontiers in oncology · 2025Article
- Takotsubo Syndrome: An International Expert Consensus Report on Practical Challenges and Specific Conditions (Part-2: Specific Entities, Risk Stratification and Challenges After Recovery)Balkan medical journal · 2024Article
- Role of miR-204 in segmental cardiac effects of phenylephrine and pressure overload.Biochemical and biophysical research communications · 2023Article
- BAG3: Nature's Quintessential Multi-Functional Protein Functions as a Ubiquitous Intra-Cellular Glue.Cells · 2023Review
- Takotsubo Syndrome: The Secret Crosstalk between Heart and Brain.Reviews in cardiovascular medicine · 2023Review
- Broken Heart Syndrome: Evolving Molecular Mechanisms and Principles of Management.Journal of clinical medicine · 2022Review
- Molecular Mechanisms of Takotsubo Syndrome.International journal of molecular sciences · 2022Review
- MicroRNA regulation of BAG3.Experimental biology and medicine (Maywood, N.J.) · 2022Review
- The role of BAG3 in health and disease: A "Magic BAG of Tricks".Journal of cellular biochemistry · 2022Review
- Autophagy in cardiovascular diseases: role of noncoding RNAs.Molecular therapy. Nucleic acids · 2021Review
- Takotsubo Syndrome: Clinical Manifestations, Etiology and Pathogenesis.Current cardiology reviews · 2021Article
- Circulating microRNAs from serum exosomes as potential biomarkers in patients with spontaneous abortion.American journal of translational research · 2021Article
- Novel Imaging and Genetic Risk Markers in Takotsubo Syndrome.Frontiers in cardiovascular medicine · 2021Review
- MiR-1165-3p Suppresses Th2 Differentiation via Targeting IL-13 and PPM1A in a Mouse Model of Allergic Airway Inflammation.Allergy, asthma & immunology research · 2020Article
- Circ-HIPK3 Strengthens the Effects of Adrenaline in Heart Failure by MiR-17-3p - ADCY6 Axis.International journal of biological sciences · 2019Article
Corrections and comments
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Authors and funding
24 authors at 7 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Molecular mechanisms protecting cardiomyocytes from stress-induced death, including tension stress, are essential for cardiac physiology and defects in these protective mechanisms can result in pathological alterations. Bcl2-associated athanogene 3 (BAG3) is expressed in cardiomyocytes and is a component of the chaperone-assisted autophagy pathway, essential for homeostasis of mechanically altered cells. BAG3 ablation in mice results in a lethal cardiomyopathy soon after birth and mutations of this gene have been associated with different cardiomyopathies including stress-induced Takotsubo cardiomyopathy (TTC). The pathogenic mechanism leading to TTC has not been defined, but it has been suggested that the heart can be damaged by excessive epinephrine (epi) spillover in the absence of a protective mechanism. The aim of this study was to provide more evidence for a role of BAG3 in the pathogenesis of TTC. Therefore, we sequenced BAG3 gene in 70 TTC patients and in 81 healthy donors with the absence of evaluable cardiovascular disease. Mutations and polymorphisms detected in the BAG3 gene included a frequent nucleotide change g2252c in the BAG3 3'-untranslated region (3'-UTR) of Takotsubo patients (P<0.05), resulting in loss of binding of microRNA-371a-5p (miR-371a-5p) as evidenced by dual-luciferase reporter assays and argonaute RNA-induced silencing complex catalytic component 2/pull-down assays. Moreover, we describe a novel signaling pathway in cardiomyocytes that leads to BAG3 upregulation on exposure to epi through an ERK-dependent upregulation of miR-371a-5p. In conclusion, the presence of a g2252c polymorphism in the BAG3 3'-UTR determines loss of miR-371a-5p binding and results in an altered response to epi, potentially representing a new molecular mechanism that contributes to TTC pathogenesis.
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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.