ArticleCardiovascular research2016
Bidirectional cross-regulation between ErbB2 and β-adrenergic signalling pathways.
Article in Cardiovascular research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 48 citations in OpenAlex.
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- Heart failure pharmacotherapy and cancer: pathways and pre-clinical/clinical evidence.European heart journal · 2024Review
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- Cardiac expression of microRNA-7 is associated with adverse cardiac remodeling.Scientific reports · 2021Article
- Doxorubicin-induced and trastuzumab-induced cardiotoxicity in mice is not prevented by metoprolol.ESC heart failure · 2021Article
- Cancer Risk in the Heart Failure Population: Epidemiology, Mechanisms, and Clinical Implications.Current oncology reports · 2020Review
- Redox Imbalances in Ageing and Metabolic Alterations: Implications in Cancer and Cardiac Diseases. An Overview from the Working Group of Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology (SIC).Antioxidants (Basel, Switzerland) · 2020Review
- From Molecular Mechanisms to Clinical Management of Antineoplastic Drug-Induced Cardiovascular Toxicity: A Translational Overview.Antioxidants & redox signaling · 2019Review
- Heart Failure and Cancer: Mechanisms of Old and New Cardiotoxic Drugs in Cancer Patients.Cardiac failure review · 2019Review
- Modern-day cardio-oncology: a report from the 'Heart Failure and World Congress on Acute Heart Failure 2018'.ESC heart failure · 2018Review
- In Vivo Imaging With Confirmation by Histopathology for Increased Rigor and Reproducibility in Translational Research: A Review of Examples, Options, and Resources.ILAR journal · 2018Article
- The Anti-Cancer Multikinase Inhibitor Sorafenib Impairs Cardiac Contractility by Reducing Phospholamban Phosphorylation and Sarcoplasmic Calcium Transients.Scientific reports · 2018Article
- Antineoplastic Drug-Induced Cardiotoxicity: A Redox Perspective.Frontiers in physiology · 2018Review
- Out of the frying pan and into the fire: damage-associated molecular patterns and cardiovascular toxicity following cancer therapy.Therapeutic advances in cardiovascular disease · 2017Review
- Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent.Circulation research · 2017Article
- Anthracyclines induce early changes in left ventricular systolic and diastolic function: A single centre study.PloS one · 2017Article
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 4 countries.
Funding
Abstract
aimsDespite the observation that ErbB2 regulates sensitivity of the heart to doxorubicin or ErbB2-targeted cancer therapies, mechanisms that regulate ErbB2 expression and activity have not been studied. Since isoproterenol up-regulates ErbB2 in kidney and salivary glands and β2AR and ErbB2 complex in brain and heart, we hypothesized that β-adrenergic receptors (AR) modulate ErbB2 signalling status. METHODS AND
resultsErbB2 transfection of HEK293 cells up-regulates β2AR, and β2AR transfection of HEK293 up-regulates ErbB2. Interestingly, cardiomyocytes isolated from myocyte-specific ErbB2-overexpressing (ErbB2(tg)) mice have amplified response to selective β2-agonist zinterol, and right ventricular trabeculae baseline force generation is markedly reduced with β2-antagonist ICI-118 551. Consistently, receptor binding assays and western blotting demonstrate that β2ARs levels are markedly increased in ErbB2(tg) myocardium and reduced by EGFR/ErbB2 inhibitor, lapatinib. Intriguingly, acute treatment of mice with β1- and β2-AR agonist isoproterenol resulted in myocardial ErbB2 increase, while inhibition with either β1- or β2-AR antagonist did not completely prevent isoproterenol-induced ErbB2 expression. Furthermore, inhibition of ErbB2 kinase predisposed mice hearts to injury from chronic isoproterenol treatment while significantly reducing isoproterenol-induced pAKT and pERK levels, suggesting ErbB2's role in transactivation in the heart.
conclusionOur studies show that myocardial ErbB2 and βAR signalling are linked in a feedback loop with βAR activation leading to increased ErbB2 expression and activity, and increased ErbB2 activity regulating β2AR expression. Most importantly, ErbB2 kinase activity is crucial for cardioprotection in the setting of β-adrenergic stress, suggesting that this mechanism is important in the pathophysiology and treatment of cardiomyopathy induced by ErbB2-targeting antineoplastic drugs.
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