Progesterone Regulates Cardiac Repolarization Through a Nongenomic Pathway: An In Vitro Patch-Clamp and Computational Modeling Study
Abstract
Background— Female sex is an independent risk factor for torsade de pointes in long-QT syndrome. In women, QT interval and torsade de pointes risk fluctuate dynamically during the menstrual cycle and pregnancy. Accumulating clinical evidence suggests a role for progesterone; however, the effect of progesterone on cardiac repolarization remains undetermined. Methods and Results— We investigated the effects of progesterone on action potential duration and membrane currents in isolated guinea pig ventricular myocytes. Progesterone rapidly shortened action potential duration, which was attributable mainly to enhancement of the slow delayed rectifier K + current (I Ks ) under basal conditions and inhibition of L-type Ca 2+ currents (I Ca,L ) under cAMP-stimulated conditions. The effects of progesterone were mediated by nitric oxide released via nongenomic activation of endothelial nitric oxide synthase; this signal transduction likely takes place in the caveolae because sucrose density gradient fractionation experiments showed colocalization of the progesterone receptor c-Src, phosphoinositide 3-kinase, Akt, and endothelial nitric oxide synthase with KCNQ1, KCNE1, and Ca V 1.2 in the caveolae fraction. We used computational single-cell and coupled-tissue action potential models incorporating the effects of progesterone on I Ks and I Ca,L ; the model reproduces the fluctuations of cardiac repolarization during the menstrual cycle observed in women and predicts the protective effects of progesterone against rhythm disturbances in congenital and drug-induced long-QT syndrome. Conclusions— Our data show that progesterone modulates cardiac repolarization by nitric oxide produced via a nongenomic pathway. A combination of experimental and computational analyses of progesterone effects provides a framework to understand complex fluctuations of QT interval and torsade de pointes risks in various hormonal states in women.
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All three studies identified through the search suggested that sex is not a significant modifier of dementia in individuals with AF.
“All three studies identified through our search suggested that sex is not a significant modifier of dementia in individuals with AF.88–90”
From Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis (2016) · cites this paper as [90]
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Cites
Calcium channel modulation by neurotransmitters, enzymes and drugs
REUTER, H. (1983) · Nature · doi:10.1038/301569a0 · Cited by 1,268 · see citing works
Female Gender as a Risk Factor for Torsades de Pointes Associated With Cardiovascular Drugs
Makkar, R. (1993) · JAMA · doi:10.1001/jama.270.21.2590 · Cited by 972 · see citing works
Mutations in the hminK gene cause long QT syndrome and suppress lKs function
Splawski, I., Tristani‐Firouzi, M., Lehmann, M. H., Sanguinetti, M. C., & Keating, M. T. (1997) · Nature Genetics · doi:10.1038/ng1197-338 · Cited by 767 · see citing works
Marx, S. O., Kurokawa, J., Reiken, S. R., Motoike, H. K., D'Armiento, J. M., Marks, A. R., & Kass, R. S. (2002) · Science · doi:10.1126/science.1066843 · Cited by 709 · see citing works
Self-citationSchwartz, P. J., Priori, S. G., Cerrone, M., Spazzolini, C., Odero, A., Napolitano, C., Bloise, R., Ferrari, G. M. D., Klersy, C., Moss, A. J., et al. (2004) · Circulation · doi:10.1161/01.cir.0000125523.14403.1e · Cited by 679 · see citing works
Locati, E. H., Zaręba, W., Moss, A. J., Schwartz, P. J., Vincent, G. M., Lehmann, M. H., Towbin, J. A., Priori, S. G., Napolitano, C., Robinson, J. L., et al. (1998) · Circulation · doi:10.1161/01.cir.97.22.2237 · Cited by 490 · see citing works
Action Potential and Contractility Changes in [Na+]i Overloaded Cardiac Myocytes: A Simulation Study
Faber, G. M., & Rudy, Y. (2000) · Biophysical Journal · doi:10.1016/s0006-3495(00)76783-x · Cited by 439 · see citing works
Long QT Syndrome and Pregnancy
Seth, R., Moss, A. J., McNitt, S. A., Zaręba, W., Andrews, M. L., Qi, M., Robinson, J. L., Goldenberg, I., Ackerman, M. J., Benhorin, J., et al. (2007) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2006.09.054 · Cited by 350 · see citing works
Regulation of a Heart Potassium Channel by Protein Kinase A and C
Walsh, K. B., & Kass, R. S. (1988) · Science · doi:10.1126/science.2845575 · Cited by 321 · see citing works
Long QT syndrome: reduced repolarization reserve and the genetic link
Roden, D. M. (2005) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2005.01589.x · Cited by 318 · see citing works
Drug-Induced QT Prolongation in Women During the Menstrual Cycle
Rodríguez, I. (2001) · JAMA · doi:10.1001/jama.285.10.1322 · Cited by 315 · see citing works
Predicting drug–hERG channel interactions that cause acquired long QT syndrome
Sanguinetti, M. C., & Mitcheson, J. S. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.01.003 · Cited by 300 · see citing works
Nontranscriptional Regulation of Cardiac Repolarization Currents by Testosterone
Bai, C., Kurokawa, J., Tamagawa, M., Nakaya, H., & Furukawa, T. (2005) · Circulation · doi:10.1161/circulationaha.104.523217 · Cited by 254 · see citing works
Self-citationThe influence of menstrual cycle phase on skeletal muscle contractile characteristics in humans
de Jonge, X. J., Boot, C. R. L., Thom, J. M., Ruell, P. A., & Thompson, M. W. (2001) · The Journal of Physiology · doi:10.1111/j.1469-7793.2001.0161m.x · Cited by 246 · see citing works
Bayaa, M., Booth, R. A., Sheng, Y., & Liu, X. J. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.220302597 · Cited by 215 · see citing works
Influence of Menstrual Cycle on QT Interval Dynamics
Nakagawa, M., Ooie, T., Takahashi, N., Taniguchi, Y., Anan, F., Yonemochi, H., & Saikawa, T. (2006) · Pacing and Clinical Electrophysiology · doi:10.1111/j.1540-8159.2006.00407.x · Cited by 174 · see citing works
Autonomic Control of Cardiac Action Potentials
Terrenoire, C., Clancy, C. E., Cormier, J. W., Sampson, K. J., & Kass, R. S. (2005) · Circulation Research · doi:10.1161/01.res.0000160555.58046.9a · Cited by 165 · see citing works
Self-citationEhring, G. R., Kerschbaum, H. H., Eder, C., Neben, A. L., Fanger, C. M., Khoury, R. M., Negulescu, P. A., & Cahalan, M. D. (1998) · The Journal of Experimental Medicine · doi:10.1084/jem.188.9.1593 · Cited by 163 · see citing works
Requirement of subunit expression for cAMP-mediated regulation of a heart potassium channel
Kurokawa, J., Chen, L., & Kass, R. S. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0434935100 · Cited by 131 · see citing works
Self-citationSpecies- and tissue-dependent effects of NO and cyclic GMP on cardiac ion channels
Fischmeister, R., Castro, L. R., Abi‐Gerges, A., Rochais, F., & Vandecasteele, G. (2005) · Comparative Biochemistry and Physiology Part A Molecular & Integrative Physiology · doi:10.1016/j.cbpb.2005.04.012 · Cited by 125 · see citing works
Bai, C., Takahashi, K., Masumiya, H., Sawanobori, T., & Furukawa, T. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705814 · Cited by 105 · see citing works
Self-citationEstrogen and Progestin Use and the QT Interval in Postmenopausal Women
Kadish, A. H., Greenland, P., Limacher, M. C., Frishman, W. H., Daugherty, S. A., & Schwartz, J. B. (2004) · Annals of Noninvasive Electrocardiology · doi:10.1111/j.1542-474x.2004.94580.x · Cited by 105 · see citing works
Furukawa, T., Bai, C., Kaihara, A., Ozaki, E., Kawano, T., Nakaya, Y., Awais, M., Sato, M., Umezawa, Y., & Kurokawa, J. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.028134 · Cited by 101 · see citing works
Self-citationK+ Channel Structure-Activity Relationships and Mechanisms of Drug-Induced QT Prolongation
Clancy, C. E., Kurokawa, J., Tateyama, M., Wehrens, X. H. T., & Kass, R. S. (2003) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.140245 · Cited by 78 · see citing works
Self-citationLilley, K. G., Epping, R., & Hafner, L. M. (1997) · PubMed · Cited by 33 · see citing works
Mendiberri, J., Rauschemberger, M. B., Sellés, J., & Massheimer, V. (2005) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.012 · Cited by 19 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
hERG K + Channels: Structure, Function, and Clinical Significance
Vandenberg, J. I., Perry, M., Perrin, M. J., Mann, S. A., Ke, Y., & Hill, A. P. (2012) · Physiological Reviews · doi:10.1152/physrev.00036.2011 · Cited by 698 · see citing works
Andrade, J. G., Aguilar, M., Atzema, C. L., Bell, A., Cairns, J. A., Cheung, C. C., Cox, J. L., Dorian, P., Gladstone, D. J., Healey, J. S., et al. (2020) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2020.09.001 · Cited by 568 · see citing works
Atrial fibrillation in women: epidemiology, pathophysiology, presentation, and prognosis
Ko, D., Rahman, F., Schnabel, R. B., Yin, X., Benjamin, E. J., & Christophersen, I. E. (2016) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2016.45 · Cited by 353 · see citing works
Varró, A., Tomek, J., Nagy, N., Virág, L., Passini, E., Rodríguez, B., & Baczkó, I. (2020) · Physiological Reviews · doi:10.1152/physrev.00024.2019 · Cited by 219 · see citing works
Molecular Pathophysiology of Congenital Long QT Syndrome
Bohnen, M. S., Peng, G., Robey, S., Terrenoire, C., Iyer, V. R., Sampson, K. J., & Kass, R. S. (2016) · Physiological Reviews · doi:10.1152/physrev.00008.2016 · Cited by 173 · see citing works
Caveolae, ion channels and cardiac arrhythmias
Balijepalli, R. C., & Kamp, T. J. (2008) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2009.01.012 · Cited by 170 · see citing works
Sex Hormones and the QT Interval: A Review
Sedlak, T., SHUFELT, C. L., Iribarren, C., & Merz, C. N. B. (2012) · Journal of Women s Health · doi:10.1089/jwh.2011.3444 · Cited by 148 · see citing works
Sex differences in mechanisms of cardiac excitation–contraction coupling
Parks, R. J., & Howlett, S. E. (2013) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-013-1233-0 · Cited by 148 · see citing works
Kurokawa, J., Tamagawa, M., Harada, N., Honda, S., Bai, C., Nakaya, H., & Furukawa, T. (2008) · The Journal of Physiology · doi:10.1113/jphysiol.2007.150367 · Cited by 148 · see citing works
Self-citationTadros, R., Ton, A., Fiset, C., & Nattel, S. (2014) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2014.03.032 · Cited by 142 · see citing works
Wong, G. R., Nalliah, C. J., Lee, G., Voskoboinik, A., Chieng, D., Prabhu, S., Parameswaran, R., Sugumar, H., Al-Kaisey, A., McLellan, A., et al. (2021) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.121.009925 · Cited by 112 · see citing works
Sex Differences in Atrial Fibrillation
Andrade, J. G., Deyell, M. W., Lee, A. K. Y., & Macle, L. (2017) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.11.022 · Cited by 99 · see citing works
Harvey, R. D., & Calaghan, S. C. (2011) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2011.07.007 · Cited by 97 · see citing works
Influence of steroid hormones on ventricular repolarization
Salem, J., Alexandre, J., Bachelot, A., & Funck‐Brentano, C. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.07.005 · Cited by 96 · see citing works
Clinical and Genetic Determinants of Torsade de Pointes Risk
Sauer, A. J., & Newton‐Cheh, C. (2012) · Circulation · doi:10.1161/circulationaha.111.080887 · Cited by 93 · see citing works
Sex differences in heart: from basics to clinics
Prajapati, C., Koivumäki, J. T., Pekkanen-Mattila, M., & Aalto‐Setälä, K. (2022) · European journal of medical research · doi:10.1186/s40001-022-00880-z · Cited by 92 · see citing works
Costa, S., Saguner, A. M., Gasperetti, A., Akdiş, D., Brunckhorst, C., & Duru, F. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.644279 · Cited by 82 · see citing works
Sex hormonal regulation of cardiac ion channels in drug-induced QT syndromes
Kurokawa, J., Kodama, M., Clancy, C. E., & Furukawa, T. (2016) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2016.09.004 · Cited by 78 · see citing works
Self-citationState of Panax ginseng Research: A Global Analysis
Xu, W., Choi, H., & Huang, L. (2017) · Molecules · doi:10.3390/molecules22091518 · Cited by 78 · see citing works
Buber, J., Mathew, J. S., Moss, A. J., Hall, W. J., Barsheshet, A., McNitt, S. A., Robinson, J. L., Zaręba, W., Ackerman, M. J., Kaufman, E. S., et al. (2011) · Circulation · doi:10.1161/circulationaha.110.000620 · Cited by 77 · see citing works
Gender disparity in cardiac electrophysiology: Implications for cardiac safety pharmacology
Jonsson, M. K. B., Vos, M. A., Duker, G., Demolombe, S., & van Veen, T. A. B. (2010) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2010.04.002 · Cited by 76 · see citing works
Acute Effects of Sex Steroid Hormones on Susceptibility to Cardiac Arrhythmias: A Simulation Study
Yang, P.-C., Kurokawa, J., Furukawa, T., & Clancy, C. E. (2010) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000658 · Cited by 75 · see citing works
Self-citationPregnenolone sulphate-independent inhibition of TRPM3 channels by progesterone
Majeed, Y., Tumova, S., Green, B. L., Seymour, V. A. L., Woods, D., Agarwal, A. K., Naylor, J., Jiang, S., Picton, H. M., Porter, K. E., et al. (2011) · Cell Calcium · doi:10.1016/j.ceca.2011.09.005 · Cited by 75 · see citing works
Computational approaches to understand cardiac electrophysiology and arrhythmias
Roberts, B. N., Yang, P., Vaughn‐Behrens, S. B., Moreno, J. D., & Clancy, C. E. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01081.2011 · Cited by 75 · see citing works
Self-citationEffect of Female Sex on Cardiac Arrhythmias
Gowd, B. M. P., & Thompson, P. D. (2012) · Cardiology in Review · doi:10.1097/crd.0b013e318259294b · Cited by 75 · see citing works
Redox- and Calmodulin-dependent S-Nitrosylation of the KCNQ1 Channel
Asada, K., Kurokawa, J., & Furukawa, T. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m807158200 · Cited by 74 · see citing works
Self-citationSalerni, S., Francescomarino, S. D., Dessalvi, C. C., Acquistapace, F., Maffei, S., & Gallina, S. (2015) · European Journal of Clinical Investigation · doi:10.1111/eci.12447 · Cited by 70 · see citing works
Yang, P., & Clancy, C. E. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00360 · Cited by 70 · see citing works
Self-citationYang, X., Chen, G., Papp, R., DeFranco, D. B., Zeng, F., & Salama, G. (2011) · The Journal of Physiology · doi:10.1113/jphysiol.2011.219501 · Cited by 69 · see citing works
Long QT syndrome: beyond the causal mutation
Amin, A. S., Pinto, Y. M., & Wilde, A. A. M. (2013) · The Journal of Physiology · doi:10.1113/jphysiol.2013.254920 · Cited by 65 · see citing works
Computational Models Reduce Complexity and Accelerate Insight Into Cardiac Signaling Networks
Yang, J. H., & Saucerman, J. J. (2011) · Circulation Research · doi:10.1161/circresaha.110.223602 · Cited by 64 · see citing works
Estrogen and calcium handling proteins: new discoveries and mechanisms in cardiovascular diseases
Jiao, L., Machuki, J. O., Wu, Q., Shi, M., Fu, L., Adekunle, A. O., Tao, X., Xu, C., Hu, X., Yin, Z., et al. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00734.2019 · Cited by 64 · see citing works
PDK4 Inhibits Cardiac Pyruvate Oxidation in Late Pregnancy
Liu, L. X., Rowe, G. C., Yang, S. H., Li, J., Damilano, F., Chan, M. C., Lu, W., Jang, C., Wada, S., Morley, M. P., et al. (2017) · Circulation Research · doi:10.1161/circresaha.117.311456 · Cited by 63 · see citing works
Multiscale Modeling in the Clinic: Drug Design and Development
Clancy, C. E., An, G., Cannon, W. R., Liu, Y., May, E. E., Ortoleva, P., Popel, A. S., Sluka, J. P., Su, J., Vicini, P., et al. (2016) · Annals of Biomedical Engineering · doi:10.1007/s10439-016-1563-0 · Cited by 62 · see citing works
Self-citationTOMPKINS, C. M., Kutyifa, V., Arshad, A., McNitt, S. A., Polonsky, B., Wang, P. J., Moss, A. J., & Zaręba, W. (2015) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12701 · Cited by 54 · see citing works
Yang, P., Perissinotti, L. L., López, F. M., Wang, Y., DeMarco, K. R., Jeng, M.-T., Vorobyov, I. V., Harvey, R. D., Kurokawa, J., Noskov, S. Y., et al. (2017) · The Journal of Physiology · doi:10.1113/jp273142 · Cited by 49 · see citing works
Self-citationHormones and sex differences: changes in cardiac electrophysiology with pregnancy
Bett, G. C. L. (2016) · Clinical Science · doi:10.1042/cs20150710 · Cited by 48 · see citing works
Wu, Z., Yu, D., Soong, T. W., Dawe, G. S., & Bian, J. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.198853 · Cited by 44 · see citing works
Genotype‐Specific Risk Stratification and Management of Patients with Long QT Syndrome
Barsheshet, A., Dotsenko, O., & Goldenberg, I. (2013) · Annals of Noninvasive Electrocardiology · doi:10.1111/anec.12117 · Cited by 43 · see citing works
In silicoprediction of drug therapy in catecholaminergic polymorphic ventricular tachycardia
Yang, P., Moreno, J. D., Miyake, C. Y., Vaughn‐Behrens, S. B., Jeng, M.-T., Grandi, E., Wehrens, X. H. T., Noskov, S. Y., & Clancy, C. E. (2015) · The Journal of Physiology · doi:10.1113/jp271282 · Cited by 41 · see citing works
Self-citationKararigas, G., Becher, E., Mahmoodzadeh, S., Knosalla, C., Hetzer, R., & Regitz‐Zagrosek, V. (2010) · Biology of Sex Differences · doi:10.1186/2042-6410-1-2 · Cited by 41 · see citing works
Effects of Sex Hormones on Cardiac Repolarization
Yang, P., & Clancy, C. E. (2010) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181d6f7dd · Cited by 39 · see citing works
Self-citationSordillo, P. P., Sordillo, D. C., & Helson, L. (2015) · PubMed · Cited by 39 · see citing works
Vedel, C., Larsen, H., Holmskov, A., Andreasen, K. R., Uldbjerg, N., Ramb, J., Bødker, B., Skibsted, L., Sperling, L., Krebs, L., et al. (2016) · Ultrasound in Obstetrics and Gynecology · doi:10.1002/uog.15948 · Cited by 39 · see citing works
Non-genomic Action of Sex Steroid Hormones and Cardiac Repolarization
Kurokawa, J., & Furukawa, T. (2013) · Biological and Pharmaceutical Bulletin · doi:10.1248/bpb.b212021 · Cited by 38 · see citing works
Self-citationTäubel, J., Prasad, K., Rosano, G. M. C., Ferber, G., Wibberley, H., Cole, S. T., Langenhoven, L. V., Fernandes, S. I., Djumanov, D., & Sugiyama, A. (2019) · The Journal of Clinical Pharmacology · doi:10.1002/jcph.1534 · Cited by 38 · see citing works
Ischemic stroke across sexes: What is the status quo?
Liberale, L., Carbone, F., Montecucco, F., Gebhard, C., Lüscher, T. F., Wegener, S., & Camici, G. G. (2018) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2018.05.001 · Cited by 37 · see citing works
Trayanova, N. A., O’Hara, T., Bayer, J. D., Boyle, P. M., McDowell, K. S., Constantino, J. L., Arevalo, H., Hu, Y., & Vadakkumpadan, F. (2012) · EP Europace · doi:10.1093/europace/eus277 · Cited by 36 · see citing works
Impact of KCNE subunits on KCNQ1 (Kv7.1) channel membrane surface targeting
Roura‐Ferrer, M., Solé, L., Oliveras, A., Dahan, R., Bielańska, J., Villarroel, Á., Comes, N., & Felipe, A. (2010) · Journal of Cellular Physiology · doi:10.1002/jcp.22265 · Cited by 36 · see citing works
Gender Differences in Arrhythmias: Focused on Atrial Fibrillation
Tian, X., Xu, Y., & Yang, Y. (2019) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-019-09918-w · Cited by 35 · see citing works
Congenital Long QT Syndromes: Prevalence, Pathophysiology and Management
Barsheshet, A., Dotsenko, O., & Goldenberg, I. (2014) · Pediatric Drugs · doi:10.1007/s40272-014-0090-4 · Cited by 35 · see citing works
Feridooni, H. A., MacDonald, J. K., Ghimire, A., Pyle, W. G., & Howlett, S. E. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00073.2016 · Cited by 34 · see citing works
Prolonged QT Interval in Cirrhosis: Twisting Time?
Lee, W., Vandenberk, B., Raj, S. R., & Lee, S. S. (2022) · Gut and Liver · doi:10.5009/gnl210537 · Cited by 31 · see citing works
Atrial fibrillation and female sex
Anselmino, M., Battaglia, A., Gallo, C., Gili, S., Matta, M., Castagno, D., Ferraris, F., Giustetto, C., & Gaïta, F. (2015) · Journal of Cardiovascular Medicine · doi:10.2459/jcm.0000000000000239 · Cited by 31 · see citing works
Gender Differences in Cardiac Repolarization Following Intravenous Sotalol Administration
Somberg, J. C., Preston, R. A., Ranade, V., Cvetanovic, I., & Molnár, J. (2011) · Journal of Cardiovascular Pharmacology and Therapeutics · doi:10.1177/1074248411406505 · Cited by 31 · see citing works
Computational Cardiology: The Heart of the Matter
Trayanova, N. A. (2012) · ISRN Cardiology · doi:10.5402/2012/269680 · Cited by 30 · see citing works
Influence of progesterone on endometrial nitric oxide synthase expression
Khorram, O., & Han, G. (2008) · Fertility and Sterility · doi:10.1016/j.fertnstert.2008.05.019 · Cited by 30 · see citing works
Influence of Oral Progesterone Administration on Drug-Induced QT Interval Lengthening
Tisdale, J. E., Jaynes, H. A., Overholser, B. R., Sowinski, K. M., Flockhart, D. A., & Kovacs, R. J. (2016) · JACC. Clinical electrophysiology · doi:10.1016/j.jacep.2016.02.015 · Cited by 30 · see citing works
Ahrens‐Nicklas, R. C., Clancy, C. E., & Christini, D. J. (2009) · Cardiovascular Research · doi:10.1093/cvr/cvp083 · Cited by 28 · see citing works
Self-citationBalycheva, M., Faggian, G. G., Glukhov, A. V., & Gorelik, J. (2015) · Biophysical Reviews · doi:10.1007/s12551-014-0159-x · Cited by 27 · see citing works
Gemmell, P. M., Burrage, K., Rodríguez, B., & Quinn, T. A. (2016) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2016.06.003 · Cited by 27 · see citing works
Kurokawa, J., Suzuki, T., & Furukawa, T. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08r23fm · Cited by 26 · see citing works
Self-citationProgesterone modulates SERCA2a expression and function in rabbit cardiomyocytes
Moshal, K. S., Zhang, Z., Roder, K., Kim, T. Y., Cooper, L. L., Litvinov, B. P., Lu, Y., Reddy, V., Terentyev, D. A., Choi, B., et al. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00127.2014 · Cited by 25 · see citing works
Sakamoto, K., & Kurokawa, J. (2019) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2019.02.009 · Cited by 25 · see citing works
Self-citationSexual Dimorphisms, Anti-Hormonal Therapy and Cardiac Arrhythmias
Grouthier, V., Moey, M. Y. Y., Gandjbakhch, E., Waintraub, X., Funck-Brentano, C., Bachelot, A., & Salem, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22031464 · Cited by 19 · see citing works
Jiang, M., Wang, Y., & Tseng, G. (2017) · Circulation Arrhythmia and Electrophysiology · doi:10.1161/circep.117.005084 · Cited by 22 · see citing works
Neurohormonal Regulation of Cardiac Ion Channels in Chronic Heart Failure
Kurokawa, J., & Abriel, H. (2009) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e3181b2b6d4 · Cited by 22 · see citing works
Self-citationOka, Y., Itoh, H., Ding, W., Shimizu, W., Makiyama, T., Ohno, S., Nishio, Y., Sakaguchi, T., Miyamoto, A., Kawamura, M., et al. (2010) · Circulation Journal · doi:10.1253/circj.cj-10-0498 · Cited by 22 · see citing works
Walters, T. E., Teh, A. W., Spence, S. J., Morton, J. B., Kistler, P. M., & Kalman, J. M. (2014) · Journal of Cardiovascular Electrophysiology · doi:10.1111/jce.12465 · Cited by 22 · see citing works
Boriani, G., Lorenzetti, S., Cerbai, E., Oreto, G., Bronzetti, G., Malavasi, V. L., Biffi, A., Padeletti, L., Botto, G., & Diemberger, I. (2017) · EP Europace · doi:10.1093/europace/eux068 · Cited by 21 · see citing works
Coyan, F. C., Abderemane-Ali, F., Amarouch, M., Piron, J., Mordel, J., Nicolas, C. S., Steenman, M., Mérot, J., Marionneau, C., Thomas, A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0093255 · Cited by 20 · see citing works
Taniguchi, T., Uesugi, M., Arai, T., Yoshinaga, T., Miyamoto, N., & Sawada, K. (2011) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318245e0c5 · Cited by 20 · see citing works
Ma, J., Hong, K., & Wang, H. (2017) · Endocrinology · doi:10.1210/en.2016-1702 · Cited by 20 · see citing works
Cheng, J., Ma, X., Zhang, J., & Su, D. (2011) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2010.00911.x · Cited by 19 · see citing works
A Receptor-Independent Effect of Estrone Sulfate on the hERG Channel
Kakusaka, S., Asayama, M., Kaihara, A., Sasano, T., Suzuki, T., Kurokawa, J., & Furukawa, T. (2009) · Journal of Pharmacological Sciences · doi:10.1254/jphs.08257sc · Cited by 19 · see citing works
Self-citationSex and Gender Aspects in Antiarrhythmic Therapy
Kurokawa, J., Kodama, M., Furukawa, T., & Clancy, C. E. (2012) · Handbook of experimental pharmacology · doi:10.1007/978-3-642-30726-3_12 · Cited by 18 · see citing works
Self-citationTisdale, J. E., Overholser, B. R., Wroblewski, H. A., & Sowinski, K. M. (2010) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2010.01869.x · Cited by 17 · see citing works
Atrial fibrillation in pregnancy: a growing challenge
Katsi, V. K., Georgiopoulos, G. A., Marketou, M. E., Oikonomou, D., PARTHENAKIS, F. I., Makris, T. K., Nihoyannopoulos, P., Vardas, P. E., & Tousoulis, D. (2017) · Current Medical Research and Opinion · doi:10.1080/03007995.2017.1330257 · Cited by 17 · see citing works
Use of oral contraceptives in women with congenital long QT syndrome
Goldenberg, I., Younis, A., Huang, D. T.-C., Yoruk, A., Rosero, S. Z., Cutter, K., Kutyifa, V., McNitt, S. A., Sotoodehnia, N., Kudenchuk, P. J., et al. (2021) · Heart Rhythm · doi:10.1016/j.hrthm.2021.07.058 · Cited by 17 · see citing works
Gender-based differences in cardiac disease
Yang, P.-C., & Clancy, C. E. (2011) · Journal of Biomedical Research · doi:10.1016/s1674-8301(11)60010-9 · Cited by 16 · see citing works
Self-citationFurushima, H., Chinushi, M., Sato, A., Aizawa, Y., Kikuchi, A., Takakuwa, K., & Tanaka, K. (2010) · Journal of Cardiovascular Electrophysiology · doi:10.1111/j.1540-8167.2010.01758.x · Cited by 15 · see citing works
Ozawa, J., Ohno, S., Hisamatsu, T., Itoh, H., Makiyama, T., Suzuki, H., Saitoh, A., & Horie, M. (2016) · Circulation Journal · doi:10.1253/circj.cj-15-0933 · Cited by 15 · see citing works
Hormonal Signaling Actions on Kv7.1 (KCNQ1) Channels
Thompson, E., Eldstrom, J., & Fedida, D. (2020) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010919-023645 · Cited by 14 · see citing works
Giammarino, L., Matas, L., Alerni, N., Horváth, A., Vashanthakumar, V., Nimani, S., Barbieri, M., Bains, S., López, R., Louradour, J., et al. (2025) · Cardiovascular Research · doi:10.1093/cvr/cvaf074 · Cited by 14 · see citing works
Molecular basis and tissue specificity of the progestin effect
Shchelkunova, T. A., & Morozov, I. A. (2015) · Molecular Biology · doi:10.1134/s0026893315050155 · Cited by 14 · see citing works
Sex Chromosomes and Sex Hormones: Dissecting the Forces That Differentiate Female and Male Hearts
Brong, A., & Kontrogianni‐Konstantopoulos, A. (2025) · Circulation · doi:10.1161/circulationaha.124.069493 · Cited by 13 · see citing works
Vicente, J., Simlund, J., Johannesen, L., Sundh, F., Florian, J. A., Ugander, M., Wagner, G. S., Woosley, R. L., & Strauss, D. G. (2015) · Journal of Electrocardiology · doi:10.1016/j.jelectrocard.2015.03.011 · Cited by 13 · see citing works
Arrhythmia in Cardiomyopathy: Sex and Gender Differences
Kim, S. K., Bennett, R. G., Ingles, J., Kumar, S., & Zaman, S. J. (2021) · Current Heart Failure Reports · doi:10.1007/s11897-021-00531-0 · Cited by 13 · see citing works
Progesterone inhibits L‐type calcium currents in gallbladder smooth muscle cells
Wu, Z., & Shen, W. (2010) · Journal of Gastroenterology and Hepatology · doi:10.1111/j.1440-1746.2010.06299.x · Cited by 13 · see citing works
Cycling matters: Sex hormone regulation of vascular potassium channels
Baldwin, S. N., Jepps, T. A., & Greenwood, I. A. (2023) · Channels · doi:10.1080/19336950.2023.2217637 · Cited by 12 · see citing works
Giudicessi, J. R., Brost, B. C., Traynor, K. D., & Ackerman, M. J. (2012) · Heart Rhythm · doi:10.1016/j.hrthm.2012.02.006 · Cited by 12 · see citing works
Oral contraceptive use and the risk of cardiac events in patients with long QT syndrome
Abu-Zeitone, A., Peterson, D. R., Polonsky, B., McNitt, S. A., & Moss, A. J. (2014) · Heart Rhythm · doi:10.1016/j.hrthm.2014.04.016 · Cited by 12 · see citing works
Wilson, Z. T., Jiang, M., Geng, J., Kaur, S., Workman, S. W., Hao, J., Bernaś, T., & Tseng, G. (2021) · The Journal of Physiology · doi:10.1113/jp281773 · Cited by 12 · see citing works
Computational models for predictive cardiac ion channel pharmacology
Yarov-Yarovoy, V. M., Allen, T. W., & Clancy, C. E. (2014) · Drug Discovery Today Disease Models · doi:10.1016/j.ddmod.2014.04.001 · Cited by 12 · see citing works
Self-citationHuang, W., Sun, H., Xiong, S., Luo, Y., Tang, Y., Zhang, Z., & Liu, H. (2024) · European journal of medical research · doi:10.1186/s40001-024-01952-y · Cited by 11 · see citing works
Metapristone (RU486 metabolite) suppresses NSCLC by targeting EGFR-mediated PI3K/AKT pathway
Shao, J., Zheng, G., Chen, H., Liu, J., Xu, A., Chen, F., Li, T., Lu, Y., Xu, J., Zheng, N., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.18640 · Cited by 10 · see citing works
Self-citationVicent, L., Méndez-Zurita, F., Viñolas, X., Alonso‐Martín, C., Abós, C. M., Pàmies, J., Alcalde, R. O., Juárez, M., Bruña, V., Devesa, C., et al. (2019) · Heart and Vessels · doi:10.1007/s00380-019-01454-6 · Cited by 10 · see citing works
The Influence of Gender on Heart Rhythm Disease
Fusco, S. A. D., Palazzo, S., Colivicchi, F., Santini, M., & the World Society of Arrhythmias (2014) · Pacing and Clinical Electrophysiology · doi:10.1111/pace.12369 · Cited by 10 · see citing works
Tabo, M., Komatsu, R., Isobe, T., Honda, M., Yamada, Y., & Kimura, K. (2010) · The Journal of Toxicological Sciences · doi:10.2131/jts.35.687 · Cited by 10 · see citing works
Influence of Menstrual Cycle on P Wave Dispersion
Karabağ, T., Hancı, V., Aydın, M., Doğan, S. M., Turan, İ. Ö., Yıldırım, N., & Güdül, N. E. (2011) · International Heart Journal · doi:10.1536/ihj.52.23 · Cited by 10 · see citing works
- Authors
- Nakamura, H., Kurokawa, J., Bai, C.-X., Asada, K., Xu, J., Oren, R. V., Zhu, Z. I., Clancy, C. E., Isobe, M., & Furukawa, T.
- Affiliations
- Cornell University (US)
- ORCID
- Venue
- Circulation
- Published
- 2007-12-18
- Volume
- 116
- Issue
- 25
- Pages
- 2913-2922
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2128601322
- Cited by
- 190
- References
- 26
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 9 · 2020: 15 · 2019: 8 · 2018: 5 · 2017: 14 · 2016: 15 · 2015: 11 · 2014: 15 · 2013: 9 · 2012: 14
- FWCI
- 7.49
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL085592)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ion channel regulation and function
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Arrhythmias and Treatments
- Keywords
- progesterone, cardiac repolarization, long QT syndrome, torsades de pointes, non-genomic signaling, nitric oxide, endothelial nitric oxide synthase, slow delayed rectifier potassium current, L-type calcium current, action potential duration, ventricular myocytes, caveolae, menstrual cycle, pregnancy, KCNQ1, KCNE1
- MeSH terms
- Action Potentials, Cyclic AMP, Animals, Female, Guinea Pigs, Long QT Syndrome, Models, Cardiovascular, Myocardial Contraction, Nitric Oxide, Progesterone, Sex Factors, Potassium Channels, Signal Transduction, Torsades de Pointes, Patch-Clamp Techniques, Computational Biology, Myocytes, Cardiac, In Vitro Techniques
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