ArticleEuropean heart journal2016
Estradiol regulates human QT-interval: acceleration of cardiac repolarization by enhanced KCNH2 membrane trafficking.
Article in European heart journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20 citing papers in PubMed, 63 citations in OpenAlex.
- Sex-specific virtual population for the prediction and assessment of arrhythmia risk.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2026Article
- Ventricular Arrhythmia and Sudden Death Risk With Concomitant Antipsychotic and SSRI Use.JAMA network open · 2026Article
- Postpartum QT Prolongation in a Long QT Syndrome Type 1 Patient.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2025Article
- Ion channel traffic jams: the significance of trafficking deficiency in long QT syndrome.Cell discovery · 2025Review
- Effect of long-term use of antipsychotics on the ventricular repolarization index.BMC psychiatry · 2024Article
- Cycling matters: Sex hormone regulation of vascular potassium channels.Channels (Austin, Tex.) · 2023Review
- Estrogenic Modulation of Ionic Channels, Pumps and Exchangers in Airway Smooth Muscle.International journal of molecular sciences · 2023Review
- Integrated analysis of the voltage-gated potassium channel-associated gene KCNH2 across cancers.BMC bioinformatics · 2023Article
- Sex-Related Differences in Genetic Cardiomyopathies.Journal of the American Heart Association · 2022Review
- Revealing the Influences of Sex Hormones and Sex Differences in Atrial Fibrillation and Vascular Cognitive Impairment.International journal of molecular sciences · 2021Review
- Successful treatment of arrhythmia with β-blocker and flecainide combination in pregnant patients with Andersen-Tawil syndrome: A case report and literature review.Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc · 2021Review
- Sexual Dimorphisms, Anti-Hormonal Therapy and Cardiac Arrhythmias.International journal of molecular sciences · 2021Review
- Ion Channel Regulation by Sex Steroid Hormones and Vitamin D in Cancer: A Potential Opportunity for Cancer Diagnosis and Therapy.Frontiers in pharmacology · 2020Review
- Cardiovascular profile of pharmacological agents used for the management of polycystic ovary syndrome.Therapeutic advances in endocrinology and metabolism · 2019Review
- Angiotensin II Promotes KHypertension (Dallas, Tex. : 1979) · 2018Article
- The Role of Serotonin in Ventricular Repolarization in Pregnant Mice.Yonsei medical journal · 2018Article
- A multiscale computational modelling approach predicts mechanisms of female sex risk in the setting of arousal-induced arrhythmias.The Journal of physiology · 2017Article
- Prolonged QT interval and cardiac arrest after a single dose of amiodarone in a woman with Turner's syndrome.Clinical case reports · 2017Article
- Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes.Pharmacology & therapeutics · 2016Review
- Normalization of QT interval duration in a long QT syndrome patient during pregnancy and the postpartum period due to sex hormone effects on cardiac repolarization.HeartRhythm case reports · 2016Article
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Authors and funding
18 authors at 6 institutions in 2 countries.
Funding
Abstract
backgroundModulation of cardiac repolarization by sexual hormones is controversial and hormonal effects on ion channels remain largely unknown. In the present translational study, we therefore assessed the relationship between QTc duration and gonadal hormones and studied underlying mechanisms. METHODS AND
resultsWe measured hormone levels and QTc intervals in women during clomiphene stimulation for infertility and women before, during, and after pregnancy. Three heterozygous LQT-2 patients (KCNH2-p.Arg752Pro missense mutation) and two unaffected family members additionally were studied during their menstrual cycles. A comprehensive cellular and molecular analysis was done to identify the mechanisms of hormonal QT-interval regulation. High estradiol levels, but neither progesterone nor estradiol/progesterone ratio, inversely correlated with QTc. Consistent with clinical data, in vitro estradiol stimulation (60 pmol/L, 48 h) enhanced IKCNH2. This increase was mediated by estradiol receptor-α-dependent promotion of KCNH2-channel trafficking to the cell membrane. To study the underlying mechanism, we focused on heat-shock proteins. The heat-shock protein-90 (Hsp90) inhibitor geldanamycin abolished estradiol-induced increase in IKCNH2. Geldanamycin had no effect on KCNH2 transcription or translation; nor did it affect expression of estradiol receptors and chaperones. Estradiol enhanced the physical interaction of KCNH2-channel subunits with heat-shock proteins and augmented ion-channel trafficking to the membrane.
conclusionElevated estradiol levels were associated with shorter QTc intervals in healthy women and female LQT-2 patients. Estradiol acts on KCNH2 channels via enhanced estradiol-receptor-α-mediated Hsp90 interaction, augments membrane trafficking and thereby increases repolarizing current. These results provide mechanistic insights into hormonal control of human ventricular repolarization and open novel therapeutic avenues.
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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.