Dynamic Chromatin Targeting of BRD4 Stimulates Cardiac Fibroblast Activation
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Abstract
Rationale: Small molecule inhibitors of the acetyl-histone binding protein BRD4 have been shown to block cardiac fibrosis in preclinical models of heart failure (HF). However, since the inhibitors target BRD4 ubiquitously, it is unclear whether this chromatin reader protein functions in cell type-specific manner to control pathological myocardial fibrosis. Furthermore, the molecular mechanisms by which BRD4 stimulates the transcriptional program for cardiac fibrosis remain unknown. Objective: We sought to test the hypothesis that BRD4 functions in a cell-autonomous and signal-responsive manner to control activation of cardiac fibroblasts, which are the major extracellular matrix-producing cells of the heart. Methods and Results: RNA-sequencing, mass spectrometry, and cell-based assays employing primary adult rat ventricular fibroblasts demonstrated that BRD4 functions as an effector of TGF-β (transforming growth factor-β) signaling to stimulate conversion of quiescent cardiac fibroblasts into Periostin ( Postn )-positive cells that express high levels of extracellular matrix. These findings were confirmed in vivo through whole-transcriptome analysis of cardiac fibroblasts from mice subjected to transverse aortic constriction and treated with the small molecule BRD4 inhibitor, JQ1. Chromatin immunoprecipitation-sequencing revealed that BRD4 undergoes stimulus-dependent, genome-wide redistribution in cardiac fibroblasts, becoming enriched on a subset of enhancers and super-enhancers, and leading to RNA polymerase II activation and expression of downstream target genes. Employing the Sertad4 (SERTA domain-containing protein 4) locus as a prototype, we demonstrate that dynamic chromatin targeting of BRD4 is controlled, in part, by p38 MAPK (mitogen-activated protein kinase) and provide evidence of a critical function for Sertad4 in TGF-β-mediated cardiac fibroblast activation. Conclusions: These findings define BRD4 as a central regulator of the pro-fibrotic cardiac fibroblast phenotype, establish a p38-dependent signaling circuit for epigenetic reprogramming in heart failure, and uncover a novel role for Sertad4 . The work provides a mechanistic foundation for the development of BRD4 inhibitors as targeted anti-fibrotic therapies for the heart.
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Cultured human primary cardiac and dermal fibroblasts and immortalized cardiac fibroblasts were relatively poor models of human cardiac fibroblast diversity under resting or stimulated conditions.
“By contrast, cultured human primary cardiac and dermal fibroblasts and immortalized cardiac fibroblasts were relatively poor models of human cardiac fibroblast diversity under resting or stimulated (TGFβ (refs. 19,39,40), IL-1β (ref. 41)) conditions.”
From Targeting immune–fibroblast cell communication in heart failure (2024) · cites this paper as [40]
The Results section, “BRD4 inhibition blocks TGF-β-mediated cardiac fibroblast activation” (page unavailable), documents TGF-β stimulation of cultured primary adult rat ventricular fibroblasts. The cited paper therefore supports the stimulation condition, but not its application to cultured human fibroblasts. The assessment that the cultures were poor models of human cardiac fibroblast diversity is the citing authors’ own conclusion, not a finding established by this source. (LLM, conf=0.82)
Experimental — accuracy not yet measuredPrimary human cardiac fibroblasts, primary human dermal fibroblasts, and immortalized human cardiac fibroblasts were relatively poor models of human cardiac fibroblast diversity under resting or stimulated (TGFβ, IL-1β) conditions.
“In contrast, primary human cardiac fibroblasts, primary human dermal fibroblasts, and immortalized human cardiac fibroblasts were relatively poor models of human cardiac fibroblast diversity under resting or stimulated (TGFβ 20,33,34 , IL-1 β 35 ) conditions.”
From Targeting the Immune-Fibrosis Axis in Myocardial Infarction and Heart Failure (2022) · cites this paper as [34]
The Results section (‘BRD4 inhibition blocks TGF-β-mediated cardiac fibroblast activation’; page unavailable) confirms that the paper used TGF-β to stimulate cardiac fibroblasts. Those experiments used primary adult rat ventricular fibroblasts, however; the paper does not establish that the listed human cell types are poor models of human cardiac fibroblast diversity. (LLM, conf=0.84)
Experimental — accuracy not yet measuredBRD4 has specific importance in aspects of heart failure pathogenesis.
“We previously showed the specific importance of BRD4 in aspects of heart failure pathogenesis4,25.”
From Chromatin remodelling drives immune cell–fibroblast communication in heart failure (2024) · cites this paper as [25]
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Cites
Trapnell, C., Williams, B. A., Pertea, G., Mortazavi, A., Kwan, G., van Baren, M. J., Salzberg, S. L., Wold, B. J., & Pachter, L. (2010) · Nature Biotechnology · doi:10.1038/nbt.1621 · Cited by 15,556 · see citing works
Selective inhibition of BET bromodomains
Filippakopoulos, P., Qi, J., Picaud, S., Shen, Y., Smith, W. B., Fedorov, O., Morse, E. M., Keates, T., Hickman, T. T., Felletar, I., et al. (2010) · Nature · doi:10.1038/nature09504 · Cited by 4,262 · see citing works
Self-citationSelective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers
Lovén, J., Hoke, H. A., Lin, C. Y., Lau, A., Orlando, D. A., Vakoc, C. R., Bradner, J. E., Lee, T. I., & Young, R. A. (2013) · Cell · doi:10.1016/j.cell.2013.03.036 · Cited by 2,961 · see citing works
Self-citationBell, E., Ivarsson, B., & Merrill, C. (1979) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.76.3.1274 · Cited by 2,069 · see citing works
Cardiac Fibrosis: The Fibroblast Awakens
Travers, J. G., Kamal, F. A., Robbins, J., Yutzey, K. E., & Blaxall, B. C. (2016) · Circulation Research · doi:10.1161/circresaha.115.306565 · Cited by 1,596 · see citing works
Jang, M. K., Mochizuki, K., Zhou, M., Jeong, H., Brady, J. N., & Ozato, K. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.06.027 · Cited by 1,301 · see citing works
Recruitment of P-TEFb for Stimulation of Transcriptional Elongation by the Bromodomain Protein Brd4
Yang, Z., Yik, J. H. N., Chen, R., He, N., Jang, M. K., Ozato, K., & Zhou, Q. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.06.029 · Cited by 1,141 · see citing works
The role of TGF-β signaling in myocardial infarction and cardiac remodeling
Bujak, M., & Frangogiannis, N. G. (2006) · Cardiovascular Research · doi:10.1016/j.cardiores.2006.10.002 · Cited by 918 · see citing works
Fibroblast-specific TGF-β–Smad2/3 signaling underlies cardiac fibrosis
Khalil, H., Kanisicak, O., Prasad, V., Correll, R. N., Fu, X., Schips, T., Vagnozzi, R. J., Liu, R., Huynh, T., Lee, S.-J., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci94753 · Cited by 905 · see citing works
Genetic lineage tracing defines myofibroblast origin and function in the injured heart
Kanisicak, O., Khalil, H., Ivey, M. J., Karch, J. M., Maliken, B. D., Correll, R. N., Brody, M. J., Lin, S. J., Aronow, B. J., Tallquist, M. D., et al. (2016) · Nature Communications · doi:10.1038/ncomms12260 · Cited by 896 · see citing works
Mohammed, S. F., Hussain, S., Mirzoyev, S. A., Edwards, W. D., Maleszewski, J. J., & Redfield, M. M. (2015) · Circulation · doi:10.1161/circulationaha.114.009625 · Cited by 874 · see citing works
Chapuy, B., McKeown, M. R., Lin, C. Y., Monti, S., Roemer, M. G. M., Qi, J., Rahl, P. B., Sun, H. H., Yeda, K. T., Doench, J. G., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2013.11.003 · Cited by 735 · see citing works
Self-citationDı́ez, J., Querejeta, R., López, B., González, A., Larman, M., & Ubago, J. L. M. (2002) · Circulation · doi:10.1161/01.cir.0000017264.66561.3d · Cited by 636 · see citing works
NF-κB Directs Dynamic Super Enhancer Formation in Inflammation and Atherogenesis
Brown, J. D., Lin, C. Y., Duan, Q., Griffin, G., Federation, A. J., Paranal, R. M., Bair, S., Newton, G., Lichtman, A. H., Kung, A. L., et al. (2014) · Molecular Cell · doi:10.1016/j.molcel.2014.08.024 · Cited by 614 · see citing works
Self-citationRedefining the identity of cardiac fibroblasts
Tallquist, M. D., & Molkentin, J. D. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.57 · Cited by 581 · see citing works
Montesano, R., & Orci, L. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.13.4894 · Cited by 560 · see citing works
BET Bromodomains Mediate Transcriptional Pause Release in Heart Failure
Anand, P., Brown, J. D., Lin, C. Y., Qi, J., Zhang, R., Artero, P. C., Alaiti, M. A., Bullard, J., Alazem, K., Margulies, K. B., et al. (2013) · Cell · doi:10.1016/j.cell.2013.07.013 · Cited by 406 · see citing works
Self-citationConserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription
Bisgrove, D. A., Mahmoudi, T., Henklein, P., & Verdin, E. M. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0705053104 · Cited by 386 · see citing works
BET inhibitors: a novel epigenetic approach
Doroshow, D. B., Eder, J. P., & LoRusso, P. M. (2017) · Annals of Oncology · doi:10.1093/annonc/mdx157 · Cited by 378 · see citing works
Small, E. M., Thatcher, J. E., Sutherland, L. B., Kinoshita, H., Gerard, R. D., Richardson, J. A., DiMaio, J. M., Sadek, H. A., Kuwahara, K., & Olson, E. N. (2010) · Circulation Research · doi:10.1161/circresaha.110.223172 · Cited by 368 · 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
Myofibroblasts: Trust your heart and let fate decide
Davis, J., & Molkentin, J. D. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.10.019 · Cited by 339 · see citing works
Roe, J., Mercan, F., Rivera, K. D., Pappin, D., & Vakoc, C. R. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.04.011 · Cited by 332 · see citing works
Molkentin, J. D., Bugg, D., Ghearing, N., Dorn, L. E., Kim, P., Sargent, M. A., Gunaje, J. J., Otsu, K., & Davis, J. (2017) · Circulation · doi:10.1161/circulationaha.116.026238 · Cited by 284 · see citing works
Dependence of collagen remodelling on α‐smooth muscle actin expression by fibroblasts
Arora, P. D., & McCulloch, C. A. (1994) · Journal of Cellular Physiology · doi:10.1002/jcp.1041590120 · Cited by 276 · see citing works
Kaur, H., Takefuji, M., Ngai, C. Y., Carvalho, J., Bayer, J., Wietelmann, A., Poetsch, A., Hoelper, S., Conway, S. J., Möllmann, H., et al. (2016) · Circulation Research · doi:10.1161/circresaha.116.308643 · Cited by 262 · see citing works
Duan, Q., McMahon, S., Anand, P., Shah, H., Thomas, S., Salunga, H. T., Huang, Y., Zhang, R., Sahadevan, A., Lemieux, M. E., et al. (2017) · Science Translational Medicine · doi:10.1126/scitranslmed.aah5084 · Cited by 262 · see citing works
Self-citationThe crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction
Stuart, S. D. F., Jesus, N. M. D., Lindsey, M. L., & Ripplinger, C. M. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.12.024 · Cited by 249 · see citing works
Clinical trials for BET inhibitors run ahead of the science
Andrieu, G., Belkina, A. C., & Denis, G. V. (2016) · Drug Discovery Today: Technologies · doi:10.1016/j.ddtec.2016.06.004 · Cited by 247 · see citing works
BRD4 is a novel therapeutic target for liver fibrosis
Ding, N., Hah, N., Yu, R. T., Sherman, M. H., Benner, C., Leblanc, M., He, M., Liddle, C., Downes, M., & Evans, R. M. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1522163112 · Cited by 211 · see citing works
BET acetyl-lysine binding proteins control pathological cardiac hypertrophy
Spiltoir, J. I., Stratton, M. S., Cavasin, M. A., Demos-Davies, K., Reid, B. G., Qi, J., Bradner, J. E., & McKinsey, T. A. (2013) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2013.07.017 · Cited by 174 · see citing works
Self-citationThe Actin–MRTF–SRF Gene Regulatory Axis and Myofibroblast Differentiation
Small, E. M. (2012) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-012-9397-0 · Cited by 146 · see citing works
Resident fibroblast expansion during cardiac growth and remodeling
Ivey, M. J., Kuwabara, J. T., Pai, J. T., Moore, R. E., Sun, Z., & Tallquist, M. D. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2017.11.012 · Cited by 146 · see citing works
Velasquez, L. S., Sutherland, L. B., Liu, Z., Grinnell, F., Kamm, K. E., Schneider, J. W., Olson, E. N., & Small, E. M. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1316764110 · Cited by 142 · see citing works
Origins of cardiac fibroblasts
Moore-Morris, T., Cattaneo, P., Puceat, M., & Evans, S. M. (2016) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.12.031 · Cited by 139 · see citing works
Conrad, R. J., Fozouni, P., Thomas, S., Sy, H., Zhang, Q., Zhou, M., & Ott, M. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.07.025 · Cited by 136 · see citing works
Transcriptional control of cardiac fibroblast plasticity
Lighthouse, J. K., & Small, E. M. (2015) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2015.12.016 · Cited by 128 · see citing works
Tang, X., Peng, R., Phillips, J. E., Deguzman, J., Ren, Y., Apparsundaram, S., Luo, Q., Bauer, C. M. T., Fuentes, M. E., DeMartino, J. A., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.04.020 · Cited by 125 · see citing works
Zhou, B., Mu, J., Gong, Y., Lu, C., Zhao, Y., He, T., & Qin, Z. (2016) · Redox Biology · doi:10.1016/j.redox.2016.12.031 · Cited by 117 · see citing works
Tian, B., Zhao, Y., Sun, H., Zhang, Y., Yang, J., & Brasier, A. R. (2016) · American Journal of Physiology-Lung Cellular and Molecular Physiology · doi:10.1152/ajplung.00224.2016 · Cited by 114 · see citing works
Hsu, S. I., Yang, C. M., Sim, K. G., Hentschel, D. M., O'Leary, E., & Bonventre, J. V. (2001) · The EMBO Journal · doi:10.1093/emboj/20.9.2273 · Cited by 107 · see citing works
Regulation of CDK4 activity by a novel CDK4-binding protein, p34SEI-1Preprint
Sugimoto, M., Nakamura, T., Ohtani, N., Hampson, L., HAMPSON, I. N., Shimamoto, A., Furuichi, Y., Okumura, K., Niwa, S., Taya, Y., et al. (1999) · Genes & Development · doi:10.1101/gad.13.22.3027 · Cited by 105 · see citing works
Song, S., Liu, L., Yu, Y., Zhang, R., Li, Y., Cao, W., Xiao, Y., Fang, G., Li, Z., Wang, X., et al. (2018) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2018.12.002 · Cited by 100 · see citing works
Signal-Dependent Recruitment of BRD4 to Cardiomyocyte Super-Enhancers Is Suppressed by a MicroRNA
Stratton, M. S., Lin, C. Y., Anand, P., Tatman, P. D., Ferguson, B. S., Wickers, S. T., Ambardekar, A. V., Sucharov, C. C., Bradner, J. E., Haldar, S. M., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.074 · Cited by 84 · see citing works
Self-citationTargeting cardiac fibroblasts to treat fibrosis of the heart: Focus on HDACs
Schuetze, K. B., McKinsey, T. A., & Long, C. S. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.02.015 · Cited by 81 · see citing works
Self-citationTang, X., Peng, R., Ren, Y., et al. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.081661 · Cited by 80 · see citing works
Epigenetic activation and memory at a TGFB2 enhancer in systemic sclerosis
Shin, J. Y., Beckett, J. D., Bagirzadeh, R., Creamer, T. J., Shah, A. A., McMahan, Z. H., Paik, J. J., Sampedro, M., MacFarlane, E. G., Beer, M., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aaw0790 · Cited by 66 · see citing works
The case for inhibiting p38 mitogen-activated protein kinase in heart failure
Golforoush, P. A., & Marber, M. S. (2015) · Frontiers in Pharmacology · doi:10.3389/fphar.2015.00102 · Cited by 62 · see citing works
BRD4 inhibition for the treatment of pathological organ fibrosis
Stratton, M. S., Haldar, S. M., & McKinsey, T. A. (2017) · F1000Research · doi:10.12688/f1000research.11339.1 · Cited by 58 · see citing works
Self-citationBET inhibitors block pancreatic stellate cell collagen I production and attenuate fibrosis in vivo
Kumar, K., DeCant, B. T., Grippo, P. J., Hwang, R. F., Bentrem, D. J., Ebine, K., & Munshi, H. G. (2017) · JCI Insight · doi:10.1172/jci.insight.88032 · Cited by 58 · see citing works
SEI family of nuclear factors regulates p53‐dependent transcriptional activation
Watanabe‐Fukunaga, R., Iida, S., Shimizu, Y., Nagata, S., & Fukunaga, R. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2005.00881.x · Cited by 52 · see citing works
Calgaro, S., Boube, M., Cribbs, D. L., & Bourbon, H.-M. G. (2002) · Genetics · doi:10.1093/genetics/160.2.547 · Cited by 45 · see citing works
Cardiac fibroblasts: from origin to injury
Tallquist, M. D. (2017) · Current Opinion in Physiology · doi:10.1016/j.cophys.2017.08.002 · Cited by 29 · see citing works
Kusano, S., Shiimura, Y., & Eizuru, Y. (2011) · Biochimie · doi:10.1016/j.biochi.2011.05.016 · Cited by 23 · see citing works
Bennetts, J. S., Fowles, L., Berkman, J. L., van Bueren, K. L., Richman, J. M., Simpson, F., & Wicking, C. (2006) · Gene · doi:10.1016/j.gene.2006.01.027 · Cited by 21 · see citing works
Sertad1 encodes a novel transcriptional co-activator of SMAD1 in mouse embryonic hearts
Peng, Y., Zhao, S., Song, L., et al. (2013) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2013.10.127 · Cited by 13 · see citing works
Stratton, M. S., Koch, K. A., & McKinsey, T. A. (2017) · Circulation · doi:10.1161/circulationaha.117.028957 · Cited by 8 · see citing works
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Targeting immune–fibroblast cell communication in heart failure
Amrute, J. M., Luo, X., Penna, V., Yang, S., Yamawaki, T., Hayat, S., Bredemeyer, A., Jung, I.-H., Kadyrov, F. F., Heo, G. S., et al. (2024) · Nature · doi:10.1038/s41586-024-08008-5 · Cited by 298 · see citing works
A transcriptional switch governs fibroblast activation in heart disease
Alexanian, M., Przytycki, P. F., Micheletti, R., Padmanabhan, A., Ye, L., Travers, J. G., Gonzalez-Teran, B., Silva, A. C., Duan, Q., Ranade, S. S., et al. (2021) · Nature · doi:10.1038/s41586-021-03674-1 · Cited by 238 · see citing works
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Alexanian, M., Padmanabhan, A., Nishino, T., Travers, J. G., Ye, L., Pelonero, A., Lee, C. Y., Sadagopan, N., Huang, Y., Auclair, K., et al. (2024) · Nature · doi:10.1038/s41586-024-08085-6 · Cited by 140 · see citing works
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Auguste, G., Rouhi, L., Matkovich, S. J., Coarfa, C., Robertson, M. J., Czernuszewicz, G., Gurha, P., & Marian, A. J. (2020) · Journal of Clinical Investigation · doi:10.1172/jci135922 · Cited by 77 · see citing works
Defining cardiac functional recovery in end-stage heart failure at single-cell resolution
Amrute, J. M., Lai, L., Ma, P., Koenig, A. L., Kamimoto, K., Bredemeyer, A., Shankar, T. S., Kuppe, C., Kadyrov, F. F., Schulte, L. J., et al. (2023) · Nature Cardiovascular Research · doi:10.1038/s44161-023-00260-8 · Cited by 79 · see citing works
Feng, L., Wang, G., Chen, Y., He, G., Liu, B., Liu, J., Chiang, C., & Ouyang, L. (2022) · Medicinal Research Reviews · doi:10.1002/med.21859 · Cited by 65 · see citing works
Padmanabhan, A., Alexanian, M., Linares-Saldana, R., González-Terán, B., Andreoletti, G., Huang, Y., Connolly, A. J., Kim, W., Hsu, A., Duan, Q., et al. (2020) · Circulation · doi:10.1161/circulationaha.120.047753 · Cited by 60 · see citing works
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Antolic, A., Wakimoto, H., Jiao, Z., Gorham, J. M., DePalma, S. R., Lemieux, M. E., Conner, D. A., Lee, D. Y., Qi, J., Seidman, J. G., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.138687 · Cited by 41 · see citing works
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Fu, R., Zu, S.-J., Liu, Y.-J., Li, J.-C., Dang, W.-Z., Liao, L.-P., Liu, L.-P., Chen, P.-Y., Huang, H.-M., Wu, K.-H., et al. (2022) · Bioengineered · doi:10.1080/21655979.2022.2066756 · Cited by 12 · see citing works
Defining Cardiac Recovery at Single Cell Resolution
Amrute, J. M., Lai, L., Ma, P., Koenig, A. L., Kamimoto, K., Bredemeyer, A., Shankar, T. S., Kuppe, C., Kadyrov, F. F., Schulte, L. J., et al. (2022) · doi:10.1101/2022.09.11.507463 · Cited by 6 · see citing works
Wang, S., Pei, G., Shen, J., Fang, Z., Chen, T., Wang, L., Cheng, H., Li, H., Pei, H., Feng, Q., et al. (2026) · Journal of Advanced Research · doi:10.1016/j.jare.2025.04.019 · Cited by 6 · see citing works
“The persistent fibrotic response subsequently contributes to cardiac remodeling and the eventual development of heart failure [46,47].”
- Authors
- Stratton, M. S., Bagchi, R. A., Felisbino, M. B., Hirsch, R. A., Smith, H. E., Riching, A. S., Enyart, B. Y., Koch, K. A., Cavasin, M. A., Alexanian, M., Song, K., Qi, J., Lemieux, M. E., Srivastava, D., Lam, M. P. Y., Haldar, S. M., Lin, C. Y., & McKinsey, T. A.
- Affiliations
- University of Colorado Anschutz (US)
- Baylor College of Medicine (US)
- From the Department of Medicine, Division of Cardiology (M.S.S., R.A.B., M.B.F., A.S.R., B.Y.E., K.A.K., M.A.C., K.S., M.P.Y.L., T.A.M.), University of Colorado Anschutz Medical Campus, Aurora
- Gladstone Institutes (US)
- Dana-Farber Cancer Institute (US)
- Bioinfo, Plantagenet, ON, Canada (M.E.L.)
- Amgen (United States) (US)
- Corresponding author
- Stratton, Matthew S.
- Bagchi, Rushita A.
- ORCID
- Venue
- Circulation Research
- Published
- 2019-09-13
- Volume
- 125
- Issue
- 7
- Pages
- 662-677
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC7310347
- OpenAlex
- W2967233606
- Cited by
- 179
- References
- 57
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 24 · 2023: 26 · 2022: 26 · 2021: 26 · 2020: 21
- FWCI
- 13.18
- Type
- journal article
- Language
- en
- Open access
- green
- doi.org
- Locations
- Circulation Research (publishedVersion)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Science Foundation
- American Heart Association (19POST34380603, 16SFRN31400013)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (216927)
- National Institutes of Health (16SFRN31400013)
- Canadian Institutes of Health Research (FRN216927)
- National Institute on Aging (K01AG056848)
- National Heart, Lung, and Blood Institute (K99HL127302, R00HL127302, F32HL126354, R01HL147558, R01HL116848, T32HL007822, R01HL127240, R01HL141278)
- National Institute of General Medical Sciences (T32GM007635)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK119594)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Congenital heart defects research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Degradation and Inhibitors
- Keywords
- BRD4, cardiac fibroblast activation, myocardial fibrosis, heart failure, TGF-beta signaling, p38 MAPK, chromatin reader proteins, epigenetic reprogramming, JQ1, antifibrotic therapy, extracellular matrix, transverse aortic constriction
- MeSH terms
- Bromodomain Containing Proteins, Animals, Azepines, Cells, Cultured, Chromatin, Enhancer Elements, Genetic, Extracellular Matrix, Female, Fibrosis, Heart Failure, Heart Ventricles, Male, Mice, Inbred C57BL, Nuclear Proteins, Protein Binding, RNA Polymerase II, Transcription Factors, Triazoles, Cell Adhesion Molecules, Transforming Growth Factor beta, Rats, Sprague-Dawley, Epigenesis, Genetic, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Mice, Rats, Myofibroblasts, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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