Phosphodiesterase 9A controls nitric-oxide-independent cGMP and hypertrophic heart disease
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Cyclic guanosine monophosphate (cGMP) is a second messenger molecule that transduces nitric-oxide- and natriuretic-peptide-coupled signalling, stimulating phosphorylation changes by protein kinase G. Enhancing cGMP synthesis or blocking its degradation by phosphodiesterase type 5A (PDE5A) protects against cardiovascular disease. However, cGMP stimulation alone is limited by counter-adaptions including PDE upregulation. Furthermore, although PDE5A regulates nitric-oxide-generated cGMP, nitric oxide signalling is often depressed by heart disease. PDEs controlling natriuretic-peptide-coupled cGMP remain uncertain. Here we show that cGMP-selective PDE9A (refs 7, 8) is expressed in the mammalian heart, including humans, and is upregulated by hypertrophy and cardiac failure. PDE9A regulates natriuretic-peptide- rather than nitric-oxide-stimulated cGMP in heart myocytes and muscle, and its genetic or selective pharmacological inhibition protects against pathological responses to neurohormones, and sustained pressure-overload stress. PDE9A inhibition reverses pre-established heart disease independent of nitric oxide synthase (NOS) activity, whereas PDE5A inhibition requires active NOS. Transcription factor activation and phosphoproteome analyses of myocytes with each PDE selectively inhibited reveals substantial differential targeting, with phosphorylation changes from PDE5A inhibition being more sensitive to NOS activation. Thus, unlike PDE5A, PDE9A can regulate cGMP signalling independent of the nitric oxide pathway, and its role in stress-induced heart disease suggests potential as a therapeutic target.
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Phospho-PTM analysis identified PDE5A targets in heart failure therapy.
“Many technological developments have been prominent, including phospho-PTM analysis to identify PDE5A targets in heart failure therapy118”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [118]
Identification of proteoforms (genetic variations, alternatively spliced products, phosphorylation, glycosylation, oxidative and other post-translational modifications) allows cardiovascular disease sub-classification.
“Now, identification of proteoforms (e.g., genetic variations, alternatively spliced products, phosphorylation118, glycosylation119, oxidative120 and other PTMs121) allow CVD sub-classification.”
From A high-stringency blueprint of the human proteome (2020) · cites this paper as [118]
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Angiotensin-neprilysin inhibition versus enalapril in heart failure
McMurray, J. J. V., Packer, M., Desai, A. S., Gong, J., Lefkowitz, M. P., Rizkala, A. R., Rouleau, J. L., Shi, V. C., Solomon, S. D., Swedberg, K., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1409077 · Cited by 6,957 · see citing works
Conti, M., & Beavo, J. A. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060305.150444 · Cited by 1,188 · see citing works
Redfield, M. M., Chen, H. H., Borlaug, B. A., Semigran, M. J., Lee, K. L., Lewis, G. D., LeWinter, M. M., Rouleau, J. L., Bull, D. A., Mann, D. L., et al. (2013) · JAMA · doi:10.1001/jama.2013.2024 · Cited by 1,156 · see citing works
Epicardial progenitors contribute to the cardiomyocyte lineage in the developing heart
Zhou, B., Ma, Q., Rajagopal, S., Wu, S. M., Domian, I., Rivera-Feliciano, J., Jiang, D., von Gise, A., Ikeda, S., Chien, K. R., et al. (2008) · Nature · doi:10.1038/nature07060 · Cited by 1,019 · see citing works
Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy
Takimoto, E., Champion, H. C., Li, M., Belardi, D. F., Ren, S. V., Rodríguez, E. R., Bedja, D., Gabrielson, K. L., Wang, Y., & Kass, D. A. (2005) · Nature Medicine · doi:10.1038/nm1175 · Cited by 902 · see citing works
Self-citationAdvances in targeting cyclic nucleotide phosphodiesterases
Maurice, D. H., Ke, H., Ahmad, F., Wang, Y., Chung, J. H., & Manganiello, V. C. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4228 · Cited by 789 · see citing works
Low Myocardial Protein Kinase G Activity in Heart Failure With Preserved Ejection Fraction
van Heerebeek, L., Hamdani, N., Falcão‐Pires, I., Leite-Moreira, A. F., Begieneman, M. P. V., Bronzwaer, J. G. F., van der Velden, J., Stienen, G. J. M., Laarman, G. J., Somsen, G. A., et al. (2012) · Circulation · doi:10.1161/circulationaha.111.076075 · Cited by 525 · see citing works
Self-citationHeart Failure With Preserved Ejection Fraction: Mechanisms, Clinical Features, and Therapies
Sharma, K., & Kass, D. A. (2014) · Circulation Research · doi:10.1161/circresaha.115.302922 · Cited by 508 · see citing works
Self-citationOka, T., Maillet, M., Watt, A. J., Schwartz, R. J., Aronow, B. J., Duncan, S. A., & Molkentin, J. D. (2006) · Circulation Research · doi:10.1161/01.res.0000215985.18538.c4 · Cited by 424 · see citing works
A TRPC6-Dependent Pathway for Myofibroblast Transdifferentiation and Wound Healing In Vivo
Davis, J., Burr, A. R., Davis, G. F., Birnbaumer, L., & Molkentin, J. D. (2012) · Developmental Cell · doi:10.1016/j.devcel.2012.08.017 · Cited by 355 · see citing works
Isolation and Characterization of PDE9A, a Novel Human cGMP-specific Phosphodiesterase
Fisher, D. A., Smith, J. F., Pillar, J. S., Denis, S. H. S., & Cheng, J. B. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.25.15559 · Cited by 342 · see citing works
Identification and Characterization of a Novel Family of Cyclic Nucleotide Phosphodiesterases
Soderling, S. H., Bayuga, S. J., & Beavo, J. A. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.25.15553 · Cited by 288 · see citing works
Cyclic Guanosine Monophosphate Compartmentation in Rat Cardiac Myocytes
Castro, L. R., Verde, I., Cooper, D. M. F., & Fischmeister, R. (2006) · Circulation · doi:10.1161/circulationaha.105.599241 · Cited by 273 · see citing works
Seo, K., Rainer, P. P., Hahn, V. S., Lee, D.-I., Jo, S., Andersen, A., Liu, T., Xu, X., Willette, R. N., Lepore, J. J., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1308963111 · Cited by 203 · see citing works
Self-citationKoitabashi, N., Aiba, T., Hesketh, G. G., Rowell, J., Zhang, M., Takimoto, E., Tomaselli, G. F., & Kass, D. A. (2009) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2009.11.015 · Cited by 177 · see citing works
Self-citationStangherlin, A., Gesellchen, F., Zoccarato, A., Terrin, A., Fields, L. A., Berrera, M., Surdo, N. C., Craig, M. A., Smith, G. L., Hamilton, G. M., et al. (2011) · Circulation Research · doi:10.1161/circresaha.110.230698 · Cited by 166 · see citing works
Nausch, L., Ledoux, J., Bonev, A. D., Nelson, M. T., & Dostmann, W. R. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0710387105 · Cited by 164 · see citing works
Self-citationHeckman, P. R. A., Wouters, C., & Prickaerts, J. (2014) · Current Pharmaceutical Design · doi:10.2174/1381612820666140826114601 · Cited by 163 · see citing works
Kinoshita, H., Kuwahara, K., Nishida, M., Zhong, J., Rong, X., Kiyonaka, S., Kuwabara, Y., Kurose, H., Inoue, R., Mori, Y., et al. (2010) · Circulation Research · doi:10.1161/circresaha.109.208314 · Cited by 163 · see citing works
Nitric Oxide Synthases in Heart Failure
Carnicer, R., Crabtree, M. J., Sivakumaran, V., Casadei, B., & Kass, D. A. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.4824 · Cited by 163 · see citing works
Self-citationCompartmentalization of Cardiac β-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5
Takimoto, E., Belardi, D. F., Tocchetti, C. G., Vahebi, S., Cormaci, G., Ketner, E., Moens, A. L., Champion, H. C., & Kass, D. A. (2007) · Circulation · doi:10.1161/circulationaha.106.643536 · Cited by 154 · see citing works
Self-citationThe cGMP Signaling Pathway as a Therapeutic Target in Heart Failure With Preserved Ejection Fraction
Greene, S. J., Gheorghiade, M., Borlaug, B. A., Pieske, B. M., Vaduganathan, M., Burnett, J. C. J., Roessig, L., Stasch, J., Solomon, S. D., Paulus, W. J., et al. (2013) · Journal of the American Heart Association · doi:10.1161/jaha.113.000536 · Cited by 138 · see citing works
Self-citationRole of cyclic GMP in gene regulation
Pilz, R. B. (2005) · Frontiers in bioscience · doi:10.2741/1616 · Cited by 111 · see citing works
Cyclic Guanosine Monophosphate Signaling and Phosphodiesterase-5 Inhibitors in Cardioprotection
Kukreja, R. C., Salloum, F. N., & Das, A. (2012) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2011.09.086 · Cited by 105 · see citing works
Cardiac resynchronization sensitizes the sarcomere to calcium by reactivating GSK-3β
Kirk, J. A., Holewinski, R. J., Kooij, V., Agnetti, G., Tunin, R. S., Witayavanitkul, N., de Tombe, P. P., Gao, W. D., Eyk, J. E. V., & Kass, D. A. (2013) · Journal of Clinical Investigation · doi:10.1172/jci69253 · Cited by 85 · see citing works
Self-citationKleiman, R. J., Chapin, D. S., Christoffersen, C. L., Freeman, J., Fonseca, K. R., Geoghegan, K. F., Grimwood, S., Guanowsky, V., Hajós, M., Harms, J. F., et al. (2012) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.111.191353 · Cited by 84 · see citing works
Verhoest, P. R., Fonseca, K. R., Hou, X., Proulx-LaFrance, C., Corman, M. L., Helal, C. J., Claffey, M. M., Tuttle, J. B., Coffman, K. J., Liu, S., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3007799 · Cited by 74 · see citing works
Singh, G., Kuc, R. E., Maguire, J. J., Fidock, M. D., & Davenport, A. P. (2006) · Circulation Research · doi:10.1161/01.res.0000232322.06633.d3 · Cited by 66 · see citing works
Müllershausen, F., Russwurm, M., Koesling, D., & Friebe, A. (2004) · Molecular Biology of the Cell · doi:10.1091/mbc.e03-12-0890 · Cited by 40 · see citing works
Designer natriuretic peptides: a vision for the future of heart failure therapeutics
Zakeri, R., & Burnett, J. C. J. (2011) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y11-048 · Cited by 25 · see citing works
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Mechanisms of physiological and pathological cardiac hypertrophy
Nakamura, M., & Sadoshima, J. (2018) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0007-y · Cited by 1,662 · see citing works
Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction: A Multiorgan Roadmap
Shah, S. J., Kitzman, D. W., Borlaug, B. A., van Heerebeek, L., Zile, M. R., Kass, D. A., & Paulus, W. J. (2016) · Circulation · doi:10.1161/circulationaha.116.021884 · Cited by 1,003 · see citing works
Self-citationPhysiological and pathological cardiac hypertrophy
Shimizu, I., & Minamino, T. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2016.06.001 · Cited by 892 · see citing works
Tan, Y., Zhang, Z., Zheng, C., Wintergerst, K. A., Keller, B. B., & Cai, L. (2020) · Nature Reviews Cardiology · doi:10.1038/s41569-020-0339-2 · Cited by 846 · see citing works
Shah, S. J., Borlaug, B. A., Kitzman, D. W., McCulloch, A. D., Blaxall, B. C., Agarwal, R., Chirinos, J. A., Collins, S., Deo, R. C., Gladwin, M. T., et al. (2020) · Circulation · doi:10.1161/circulationaha.119.041886 · Cited by 436 · see citing works
Self-citationCellular and molecular pathobiology of heart failure with preserved ejection fraction
Mishra, S., & Kass, D. A. (2021) · Nature Reviews Cardiology · doi:10.1038/s41569-020-00480-6 · Cited by 423 · see citing works
Self-citationGorter, T. M., van Veldhuisen, D. J., Bauersachs, J. K., Borlaug, B. A., Čelutkienė, J., Coats, A. J. S., Crespo‐Leiro, M. G., Guazzi, M., Harjola, V., Heymans, S. R. B., et al. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.1029 · Cited by 396 · see citing works
Self-citationMolecular Physiology of Membrane Guanylyl Cyclase Receptors
Kühn, M. (2016) · Physiological Reviews · doi:10.1152/physrev.00022.2015 · Cited by 358 · see citing works
Heart failure with preserved ejection fraction: from mechanisms to therapies
Lam, C. S. P., Voors, A. A., de Boer, R. A., Solomon, S. D., & van Veldhuisen, D. J. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy301 · Cited by 355 · see citing works
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Baillie, G. S., Tejeda, G. S., & Kelly, M. P. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0033-4 · Cited by 348 · see citing works
Angiotensin Receptor Neprilysin Inhibition in Heart Failure With Preserved Ejection Fraction
Solomon, S. D., Rizkala, A. R., Gong, J., Wang, W., Anand, I. S., Ge, J., Lam, C. S. P., Maggioni, A. P., Martínez, F. A., Packer, M., et al. (2017) · JACC Heart Failure · doi:10.1016/j.jchf.2017.04.013 · Cited by 310 · see citing works
A high-stringency blueprint of the human proteome
Adhikari, S., Nice, E. C., Deutsch, E. W., Lane, L., Omenn, G. S., Pennington, S. R., Paik, Y.-K., Overall, C. M., Corrales, F. J., Cristea, I. M., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-19045-9 · Cited by 210 · see citing works
Dessauer, C. W., Watts, V. J., Ostrom, R. S., Conti, M., Dove, S., & Seifert, R. (2017) · Pharmacological Reviews · doi:10.1124/pr.116.013078 · Cited by 201 · see citing works
Myocardial hypertrophy and its role in heart failure with preserved ejection fraction
Heinzel, F. R., Hohendanner, F., Jin, G., Sedej, S., & Edelmann, F. (2015) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00374.2015 · Cited by 153 · see citing works
Kelly, M. P. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.11.004 · Cited by 147 · see citing works
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Loescher, C. M., Hobbach, A. J., & Linke, W. A. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab328 · Cited by 150 · see citing works
cGMP: a unique 2nd messenger molecule – recent developments in cGMP research and development
Friebe, A., Sandner, P., & Schmidtko, A. (2019) · Naunyn-Schmiedeberg s Archives of Pharmacology · doi:10.1007/s00210-019-01779-z · Cited by 137 · see citing works
Microvascular Dysfunction in Heart Failure With Preserved Ejection Fraction
D’Amario, D., Migliaro, S., Borovac, J. A., Restivo, A., Vergallo, R., Galli, M., Leone, A. M., Montone, R. A., Niccoli, G., Aspromonte, N., et al. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.01347 · Cited by 135 · see citing works
Liu, X., Xu, X. Y., Shang, R., & Chen, Y. (2018) · Nitric Oxide · doi:10.1016/j.niox.2018.06.004 · Cited by 134 · see citing works
PKG1-modified TSC2 regulates mTORC1 activity to counter adverse cardiac stress
Ranek, M. J., Kokkonen-Simon, K. M., Chen, A., Dunkerly-Eyring, B. L., Vera, M. P., Oeing, C. U., Patel, C. H., Nakamura, T., Zhu, G., Bedja, D., et al. (2019) · Nature · doi:10.1038/s41586-019-0895-y · Cited by 130 · see citing works
Self-citationVong, L. B., Bui, T. Q., Tomita, T., Sakamoto, H., Hiramatsu, Y., & Nagasaki, Y. (2018) · Biomaterials · doi:10.1016/j.biomaterials.2018.03.023 · Cited by 129 · see citing works
Panossian, A., Seo, E.-J., & Efferth, T. (2018) · Phytomedicine · doi:10.1016/j.phymed.2018.09.204 · Cited by 127 · see citing works
Cyclic nucleotide phosphodiesterases in heart and vessels: A therapeutic perspective
Bobin, P., Belacel-Ouari, M., Bedioune, I., Zhang, L., Leroy, J., Leblais, V., Fischmeister, R., & Vandecasteele, G. (2016) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2016.02.004 · Cited by 117 · see citing works
Ni, D., Lu, S., & Zhang, J. (2019) · Medicinal Research Reviews · doi:10.1002/med.21585 · Cited by 116 · see citing works
Sanders, O. D., & Rajagopal, L. (2020) · Journal of Alzheimer s Disease Reports · doi:10.3233/adr-200191 · Cited by 115 · see citing works
Bullen, J. W., Tchernyshyov, I., Holewinski, R. J., Devine, L. R., Wu, F., Venkatraman, V., KASS, D., Cole, R. N., Eyk, J. E. V., & Semenza, G. L. (2016) · Science Signaling · doi:10.1126/scisignal.aaf0583 · Cited by 107 · see citing works
Self-citationCardiac Disorders and Pathophysiology of Sarcomeric Proteins
van der Velden, J., & Stienen, G. J. M. (2018) · Physiological Reviews · doi:10.1152/physrev.00040.2017 · Cited by 109 · see citing works
What people with Down Syndrome can teach us about cardiopulmonary disease
Colvin, K. L., & Yeager, M. E. (2017) · European Respiratory Review · doi:10.1183/16000617.0098-2016 · Cited by 109 · see citing works
Proteomics Research in Cardiovascular Medicine and Biomarker Discovery
Lam, M. P. Y., Ping, P., & Murphy, E. (2016) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2016.10.031 · Cited by 107 · see citing works
Cyclic nucleotide phosphodiesterases as therapeutic targets in cardiac hypertrophy and heart failure
Kamel, R., Leroy, J., Vandecasteele, G., & Fischmeister, R. (2022) · Nature Reviews Cardiology · doi:10.1038/s41569-022-00756-z · Cited by 100 · see citing works
Nanodomain Regulation of Cardiac Cyclic Nucleotide Signaling by Phosphodiesterases
Kokkonen-Simon, K. M., & Kass, D. A. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104756 · Cited by 101 · see citing works
Self-citationRecent Developments in Heart Failure
Dassanayaka, S., & Jones, S. P. (2015) · Circulation Research · doi:10.1161/circresaha.115.305765 · Cited by 101 · see citing works
Capillary leak and endothelial permeability in critically ill patients: a current overview
Saravi, B., Goebel, U., Hassenzahl, L. O., Jung, C., David, S., Feldheiser, A., Stopfkuchen-Evans, M. F., & Wollborn, J. (2023) · Intensive Care Medicine Experimental · doi:10.1186/s40635-023-00582-8 · Cited by 100 · see citing works
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Understanding heart failure with preserved ejection fraction: where are we today?
van Heerebeek, L., & Paulus, W. J. (2016) · Netherlands Heart Journal · doi:10.1007/s12471-016-0810-1 · Cited by 97 · see citing works
Self-citationChen, S., Zhang, Y., Lighthouse, J. K., Mickelsen, D. M., Wu, J., Yao, P., Small, E. M., & Chen, Y. (2019) · Circulation · doi:10.1161/circulationaha.119.042178 · Cited by 90 · see citing works
PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction
Knight, W. E., Chen, S., Zhang, Y., Oikawa, M., Wu, M., Zhou, Q., Miller, C. L., Cai, Y., Mickelsen, D. M., Moravec, C. S., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1607728113 · Cited by 88 · see citing works
Heart failure with preserved ejection fraction: insights into diagnosis and pathophysiology
Nagueh, S. F. (2020) · Cardiovascular Research · doi:10.1093/cvr/cvaa228 · Cited by 91 · see citing works
Cyclic GMP and PKG Signaling in Heart Failure
Numata, G., & Takimoto, E. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.792798 · Cited by 85 · see citing works
Self-citationSkeletal muscle derived Musclin protects the heart during pathological overload
Szaroszyk, M., Kattih, B., Martín-Garrido, A., Trogisch, F. A., Dittrich, G. M., Grund, A., Abouissa, A., Derlin, K., Meier, M., Holler, T., et al. (2022) · Nature Communications · doi:10.1038/s41467-021-27634-5 · Cited by 86 · see citing works
Mongirdienė, A., Skrodenis, L., Varoneckaitė, L., Mierkytė, G., & Gerulis, J. (2022) · Biomedicines · doi:10.3390/biomedicines10030602 · Cited by 83 · see citing works
Zhazykbayeva, S., Pabel, S., Mügge, A., Sossalla, S. T., & Hamdani, N. (2020) · Biophysical Reviews · doi:10.1007/s12551-020-00742-0 · Cited by 83 · see citing works
Self-citationCardiac Phosphodiesterases and Their Modulation for Treating Heart Disease
Kim, G. E., & Kass, D. A. (2016) · Handbook of experimental pharmacology · doi:10.1007/164_2016_82 · Cited by 79 · see citing works
Self-citationNatriuretic peptide pathways in heart failure: further therapeutic possibilities
Sangaralingham, S. J., Kühn, M., Cannone, V., Chen, H. H., & Burnett, J. C. J. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac125 · Cited by 78 · see citing works
Vettel, C., Lindner, M., Dewenter, M., Lorenz, K., Schanbacher, C., Riedel, M., Lämmle, S., Meinecke, S., Mason, F. E., Sossalla, S. T., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.310069 · Cited by 78 · see citing works
cGMP at the centre of attention: emerging strategies for activating the cardioprotective PKG pathway
Park, M. S., Sandner, P., & Krieg, T. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0679-9 · Cited by 75 · see citing works
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Olver, T. D., Edwards, J. C., Jurrissen, T. J., Veteto, A. B., Jones, J. L., Gao, C., Rau, C., Warren, C. M., Klutho, P. J., Alex, L., et al. (2019) · JACC Basic to Translational Science · doi:10.1016/j.jacbts.2019.02.004 · Cited by 74 · see citing works
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Crocini, C., & Gotthardt, M. (2021) · Biophysical Reviews · doi:10.1007/s12551-021-00840-7 · Cited by 74 · see citing works
Buys, E. S., Zimmer, D. P., Chickering, J. G., Graul, R. M., Chien, Y., Profy, A. T., Hadcock, J. R., Masferrer, J. L., & Milne, G. T. (2018) · Nitric Oxide · doi:10.1016/j.niox.2018.05.009 · Cited by 73 · see citing works
Matsuo, A., Nagai‐Okatani, C., Nishigori, M., Kangawa, K., & Minamino, N. (2018) · Peptides · doi:10.1016/j.peptides.2018.08.006 · Cited by 73 · see citing works
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Caturano, A., Vetrano, E., Galiero, R., Salvatore, T., Docimo, G., Epifani, R., Alfano, M., Sardu, C., Marfella, R., Rinaldi, L., et al. (2022) · Reviews in Cardiovascular Medicine · doi:10.31083/j.rcm2305165 · Cited by 76 · see citing works
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Hall, G., Wang, L., & Spurney, R. F. (2019) · Cells · doi:10.3390/cells9010044 · Cited by 71 · see citing works
Höllerhage, M., Moebius, C., Melms, J. C., Chiu, W., Goebel, J. N., Chakroun, T., Koeglsperger, T., Oertel, W. H., Rösler, T. W., Bickle, M., et al. (2017) · Scientific Reports · doi:10.1038/s41598-017-11664-5 · Cited by 70 · see citing works
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Fayyaz, A. U., Eltony, M., Prokop, L. J., Koepp, K. E., Borlaug, B. A., Dasari, S., Bois, M. C., Margulies, K. B., Maleszewski, J. J., Wang, Y., et al. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-024-01067-1 · Cited by 71 · see citing works
Self-citationBaliga, R. S., Preedy, M. E. J., Dukinfield, M., Chu, S. M., Aubdool, A. A., Bubb, K. J., Moyes, A. J., Tones, M. A., & Hobbs, A. J. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800996115 · Cited by 67 · see citing works
Acute Enhancement of Cardiac Function by Phosphodiesterase Type 1 Inhibition
Hashimoto, T., Kim, G. E., Tunin, R. S., Adesiyun, T. A., Hsu, S., Nakagawa, R., Zhu, G., OʼBrien, J., Hendrick, J. P., Davis, R. E., et al. (2018) · Circulation · doi:10.1161/circulationaha.117.030490 · Cited by 67 · see citing works
Self-citationNeuraminidase 1 is a driver of experimental cardiac hypertrophy
Chen, Q., Ma, G., Liu, J., Cai, Y., Zhang, J., Wei, T., Pan, A., Jiang, S., Xiao, Y., Xiao, P., et al. (2021) · European Heart Journal · doi:10.1093/eurheartj/ehab347 · Cited by 66 · see citing works
Rainer, P. P., Dong, P., Sorge, M., Fert‐Bober, J., Holewinski, R. J., Wang, Y., Foss, C. A., An, S. S., Baracca, A., Solaini, G., et al. (2018) · Circulation Research · doi:10.1161/circresaha.117.312082 · Cited by 65 · see citing works
Self-citationPosttranslational modifications of titin from cardiac muscle: how, where, and what for?
Koser, F., Loescher, C. M., & Linke, W. A. (2019) · FEBS Journal · doi:10.1111/febs.14854 · Cited by 65 · see citing works
The NO-cGMP-PKG Axis in HFpEF: From Pathological Mechanisms to Potential Therapies
Cai, Z., Wu, C., Xu, Y., Cai, J., Zhao, M., & Zu, L. (2022) · Aging and Disease · doi:10.14336/ad.2022.0523 · Cited by 67 · see citing works
Old dog, new tricks: novel cardiac targets and stress regulation by protein kinase G
Rainer, P. P., & Kass, D. A. (2016) · Cardiovascular Research · doi:10.1093/cvr/cvw107 · Cited by 63 · see citing works
Self-citationHFpEF, a Disease of the Vasculature: A Closer Look at the Other Half
Lyle, M. A., & Brozovich, F. V. (2018) · Mayo Clinic Proceedings · doi:10.1016/j.mayocp.2018.05.001 · Cited by 63 · see citing works
Inflammatory Mechanisms in Heart Failure with Preserved Ejection Fraction
Daou, D., Gillette, T. G., & Hill, J. A. (2023) · Physiology · doi:10.1152/physiol.00004.2023 · Cited by 74 · see citing works
Effect of asymmetric dimethylarginine (ADMA) on heart failure development
Liu, X., Hou, L., Xu, D., Chen, A., Yang, L., Zhuang, Y., Xu, Y., Fassett, J. T., & Chen, Y. (2016) · Nitric Oxide · doi:10.1016/j.niox.2016.02.006 · Cited by 61 · see citing works
Distinct submembrane localisation compartmentalises cardiac NPR1 and NPR2 signalling to cGMP
Subramanian, H., Froese, A., Jönsson, P., Schmidt, H., Gorelik, J., & Nikolaev, V. O. (2018) · Nature Communications · doi:10.1038/s41467-018-04891-5 · Cited by 61 · see citing works
cGMP Signaling and Modulation in Heart Failure
Blanton, R. M. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000749 · Cited by 59 · see citing works
Chen, Y., Xu, M., Zhang, J., Ma, J., Gao, M., Zhang, Z., Xu, Y., & Liu, S. (2016) · Advanced Materials · doi:10.1002/adma.201604580 · Cited by 59 · see citing works
Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System
Ercu, M., & Klußmann, E. (2018) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd5010014 · Cited by 59 · see citing works
Brescia, M., & Zaccolo, M. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17101672 · Cited by 57 · see citing works
Shafiee-Nick, R., Afshari, A. R., Mousavi, S. H., Rafighdoust, A. A., Askari, V. R., Mollazadeh, H., Fanoudi, S., Mohtashami, E., Rahimi, V. B., Mohebbi, M., et al. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.07.084 · Cited by 57 · see citing works
Cyclic GMP modulating drugs in cardiovascular diseases: mechanism-based network pharmacology
Petraina, A., Nogales, C., Krahn, T., Mucke, H. A., Lüscher, T. F., Fischmeister, R., Kass, D. A., Burnett, J. C. J., Hobbs, A. J., & Schmidt, H. H. H. W. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab240 · Cited by 52 · see citing works
Self-citationNew Pharmacological Strategies to Increase cGMP
Buglioni, A., & Burnett, J. C. J. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-052914-091923 · Cited by 52 · see citing works
Kov́acs, Á., Alogna, A., Post, H., & Hamdani, N. (2016) · Netherlands Heart Journal · doi:10.1007/s12471-016-0814-x · Cited by 53 · see citing works
Self-citationNitric Oxide Nano-Delivery Systems for Cancer Therapeutics: Advances and Challenges
Vong, L. B., & Nagasaki, Y. (2020) · Antioxidants · doi:10.3390/antiox9090791 · Cited by 53 · see citing works
Myeloid Cell Derived IL1β Contributes to Pulmonary Hypertension in HFpEF
Agrawal, V., Kropski, J. A., Gokey, J. J., Kobeck, E., Murphy, M. B., Murray, K. T., Fortune, N. L., Moore, C. S., Meoli, D. F., Monahan, K., et al. (2023) · Circulation Research · doi:10.1161/circresaha.123.323119 · Cited by 52 · see citing works
Calamera, G., Moltzau, L. R., Levy, F. O., & Andressen, K. W. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23042145 · Cited by 51 · see citing works
Ranek, M. J., Oeing, C. U., Sanchez‐Hodge, R., Kokkonen-Simon, K. M., Dillard, D., Aslam, M., Rainer, P. P., Mishra, S., Dunkerly-Eyring, B. L., Holewinski, R. J., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-18980-x · Cited by 51 · see citing works
Self-citationMTORC1-Regulated Metabolism Controlled by TSC2 Limits Cardiac Reperfusion Injury
Oeing, C. U., Jun, S., Mishra, S., Dunkerly-Eyring, B. L., Chen, A., Martinez, M. I. G., Tahir, U. A., Gerszten, R. E., Paolocci, N., Ranek, M. J., et al. (2021) · Circulation Research · doi:10.1161/circresaha.120.317710 · Cited by 51 · see citing works
Self-citationKolijn, D., Kov́acs, Á., Herwig, M., Lódi, M., Sieme, M., Haj, A. A., Sandner, P., Papp, Z., Reusch, H. P., Haldenwang, P. L., et al. (2020) · Frontiers in Physiology · doi:10.3389/fphys.2020.00345 · Cited by 50 · see citing works
Self-citationLeveraging Signaling Pathways to Treat Heart Failure With Reduced Ejection Fraction
Pinilla-Vera, M., Hahn, V. S., & Kass, D. A. (2019) · Circulation Research · doi:10.1161/circresaha.119.313682 · Cited by 49 · see citing works
Self-citationMoghtadaei, M., Polina, I. A., & Rose, R. A. (2015) · Progress in Biophysics and Molecular Biology · doi:10.1016/j.pbiomolbio.2015.12.001 · Cited by 48 · see citing works
Nitric oxide and pulmonary arterial hypertension
Chester, A. H., Yacoub, M. H., & Moncada, S. (2017) · Global Cardiology Science and Practice · doi:10.21542/gcsp.2017.14 · Cited by 49 · see citing works
PKG1α Cysteine-42 Redox State Controls mTORC1 Activation in Pathological Cardiac Hypertrophy
Oeing, C. U., Nakamura, T., Pan, S., Mishra, S., Dunkerly-Eyring, B. L., Kokkonen-Simon, K. M., Lin, B. L., Chen, A., Zhu, G., Bedja, D., et al. (2020) · Circulation Research · doi:10.1161/circresaha.119.315714 · Cited by 48 · see citing works
Self-citationPrysyazhna, O. D., Burgoyne, J. R., Scotcher, J., Grover, S. P., Kass, D. A., & Eaton, P. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m116.724070 · Cited by 46 · see citing works
Self-citationMyocardial Phosphodiesterases and Their Role in cGMP Regulation
Dunkerly-Eyring, B. L., & Kass, D. A. (2019) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0000000000000773 · Cited by 46 · see citing works
Self-citationInhibition of phosphodiesterase type 9 reduces obesity and cardiometabolic syndrome in mice
Mishra, S., Sadagopan, N., Dunkerly-Eyring, B. L., Rodriguez, S., Sarver, D. C., Ceddia, R. P., Murphy, S. A., Knútsdóttir, H., Jani, V., Ashok, D., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci148798 · Cited by 46 · see citing works
Self-citationMyocardial reverse remodeling: how far can we rewind?
Gonçalves‐Rodrigues, P., Leite-Moreira, A. F., & Falcão‐Pires, I. (2016) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00696.2015 · Cited by 45 · see citing works
Fert-Bober, J., Murray, C. I., Parker, S. J., & Van Eyk, J. E. (2018) · Circulation Research · doi:10.1161/circresaha.118.310966 · Cited by 45 · see citing works
Molecular Screen Identifies Cardiac Myosin–Binding Protein-C as a Protein Kinase G-Iα Substrate
Thoonen, R., Giovanni, S., Govindan, S., Lee, D. I., Wang, G.-R., Calamaras, T. D., Takimoto, E., Kass, D. A., Sadayappan, S., & Blanton, R. M. (2015) · Circulation Heart Failure · doi:10.1161/circheartfailure.115.002308 · Cited by 45 · see citing works
Self-citationLi, J., Liu, C., Wei, N., Li, X., Liu, Y.-Y., Yang, R., & Jia, Y. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.011 · Cited by 45 · see citing works
From comorbidities to heart failure with preserved ejection fraction: a story of oxidative stress
Franssen, C., Chen, H. S., Hamdani, N., & Paulus, W. J. (2015) · Heart · doi:10.1136/heartjnl-2015-307787 · Cited by 45 · see citing works
Self-citationPhosphodiesterase 9a Inhibition in Mouse Models of Diastolic Dysfunction
Methawasin, M., Strom, J. G., Borkowski, T., Hourani, Z., Runyan, R. B., Smith, J. E., & Granzier, H. L. M. (2020) · Circulation Heart Failure · doi:10.1161/circheartfailure.119.006609 · Cited by 44 · see citing works
Phosphodiesterase in heart and vessels: from physiology to diseases
Fu, Q., Wang, Y., Chen, Y., & Xiang, Y. K. (2023) · Physiological Reviews · doi:10.1152/physrev.00015.2023 · Cited by 43 · see citing works
Pathophysiology of Aortic Valve Stenosis: Is It Both Fibrocalcific and Sex Specific?
Sritharen, Y., Enriquez-Sarano, M. L., Schaff, H. V., Casaclang‐Verzosa, G., & Miller, J. D. (2017) · Physiology · doi:10.1152/physiol.00025.2016 · Cited by 43 · see citing works
West, T. M., Wang, Q., Deng, B., Zhang, Y., Barbagallo, F., Reddy, G. R., Chen, D., Phan, K. S., Xu, B. Y., Isidori, A. M., et al. (2019) · Journal of the American Heart Association · doi:10.1161/jaha.119.012273 · Cited by 43 · see citing works
Lugnier, C., Meyer, A., Charloux, A., Andrès, E., Gény, B., & Talha, S. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8101746 · Cited by 43 · see citing works
A concise discussion of the regulatory role of cGMP kinase I in cardiac physiology and pathology
Hofmann, F. B. (2018) · Basic Research in Cardiology · doi:10.1007/s00395-018-0690-1 · Cited by 42 · see citing works
Chen, S., Lv, L., Zhan, Z., Wang, X., You, Z., Luo, X., & You, H. (2019) · Journal of Cellular Physiology · doi:10.1002/jcp.29382 · Cited by 42 · see citing works
Cardiac retinoic acid levels decline in heart failure
Yang, N., Parker, L. E., Yu, J., Jones, J. W., Liu, T., Papanicolaou, K. N., Talbot, C. C., Margulies, K. B., O'Rourke, B. P., Kane, M. A., et al. (2021) · JCI Insight · doi:10.1172/jci.insight.137593 · Cited by 42 · see citing works
Self-citationFRET-based cyclic GMP biosensors measure low cGMP concentrations in cardiomyocytes and neurons
Calamera, G., Li, D., Ulsund, A. H., Kim, J. J., Neely, O. C., Moltzau, L. R., Bjørnerem, M., Paterson, D. J., Kim, C., Levy, F. O., et al. (2019) · Communications Biology · doi:10.1038/s42003-019-0641-x · Cited by 42 · see citing works
- Authors
- Lee, D. I., Zhu, G., Sasaki, T., Cho, G.-S., Hamdani, N., Holewinski, R., Jo, S.-H., Danner, T., Zhang, M., Rainer, P. P., Bedja, D., Kirk, J. A., Ranek, M. J., Dostmann, W. R., Kwon, C., Margulies, K. B., Van Eyk, J. E., Paulus, W. J., Takimoto, E., & Kass, D. A.
- Affiliations
- Johns Hopkins University (US)
- Tanabe Pharma Corporation (Japan) (JP)
- Amsterdam Cardiovascular Sciences (NL)
- Cedars-Sinai Medical Center (US)
- Kangwon National University (KR)
- University of Vermont (US)
- University of Pennsylvania (US)
- Corresponding author
- Kass, David A.
- ORCID
- Venue
- Nature
- Published
- 2015-03
- Volume
- 519
- Issue
- 7544
- Pages
- 472-476
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4376609
- OpenAlex
- W2020159180
- Cited by
- 353
- References
- 30
- Citations by year
- 2026: 9 · 2025: 15 · 2024: 36 · 2023: 22 · 2022: 41 · 2021: 44 · 2020: 34 · 2019: 33 · 2018: 41 · 2017: 27 · 2016: 37 · 2015: 14
- FWCI
- 17.23
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Pure Amsterdam UMC (acceptedVersion, other-oa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- American Heart Association
- Pfizer
- University of Pennsylvania
- University of Connecticut
- Johns Hopkins University
- European Commission (261409)
- Fondation Leducq (HL-093432)
- Österreichischen Akademie der Wissenschaften
- National Institutes of Health (HHSN268201000032C, n01hv28180-13-0-0, HL-07227, HL089847)
- National Heart, Lung, and Blood Institute (NHLBI-HV-10-05, HL089297, R01HL093432, HL-07227, N01 HV028180, HHS-N268201000032C, R01HL119012, HL105993, HL093432, HL-119012, HL-68891, HL089847, P01HL107153, R01HL089297, R01HL089847, R01HL111198, R01HL105993, T32HL007227, R01HL068891)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Phosphodiesterase function and regulation
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- PDE9A, PDE5A, cGMP signaling, cardiac hypertrophy, heart failure, pressure overload, cardiomyocytes, protein kinase G, heart disease treatment, nitric oxide synthase, neurohormones, cardiomyopathy
- MeSH terms
- Animals, Aortic Valve Stenosis, Cyclic GMP, Cardiomegaly, Humans, Male, Mice, Inbred C57BL, Myocardium, Nitric Oxide, Phosphodiesterase Inhibitors, Pressure, Stress, Physiological, 3',5'-Cyclic-AMP Phosphodiesterases, Signal Transduction, Up-Regulation, Nitric Oxide Synthase, Muscle Cells, Natriuretic Peptides, Mice
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