Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico.
- Autores:
-
Llamas Nieves, Andrés Elías
Lozada Martínez, Ivan David
Torres Llinás, Daniela Marcela
Manzur Jattin, Fernando
Cardales Periñán, Miguel
- Tipo de recurso:
- Article of journal
- Fecha de publicación:
- 2021
- Institución:
- Universidad de Cartagena
- Repositorio:
- Repositorio Universidad de Cartagena
- Idioma:
- eng
- OAI Identifier:
- oai:repositorio.unicartagena.edu.co:11227/13457
- Acceso en línea:
- https://doi.org/10.32997/rcb-2021-3371
- Palabra clave:
- Renin-Angiotensin system
Angiotensin II
Cardiovascular diseases
Cardiac arrhythmias
Angiotensina II
Fibrilación auricular
Sistema Renina-Angiotensina
Enfermedades cardiovasculares
Arritmias cardiacas
- Rights
- openAccess
- License
- Andrés Elías Llamas Nieves - 2021
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dc.title.spa.fl_str_mv |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
dc.title.translated.eng.fl_str_mv |
News on angiotensin II and atrial fibrillation : from the molecular to the pathophysiological. |
title |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
spellingShingle |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. Renin-Angiotensin system Angiotensin II Cardiovascular diseases Cardiac arrhythmias Angiotensina II Fibrilación auricular Sistema Renina-Angiotensina Enfermedades cardiovasculares Arritmias cardiacas |
title_short |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
title_full |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
title_fullStr |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
title_full_unstemmed |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
title_sort |
Novedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico. |
dc.creator.fl_str_mv |
Llamas Nieves, Andrés Elías Lozada Martínez, Ivan David Torres Llinás, Daniela Marcela Manzur Jattin, Fernando Cardales Periñán, Miguel |
dc.contributor.author.spa.fl_str_mv |
Llamas Nieves, Andrés Elías Lozada Martínez, Ivan David Torres Llinás, Daniela Marcela Manzur Jattin, Fernando Cardales Periñán, Miguel |
dc.subject.eng.fl_str_mv |
Renin-Angiotensin system Angiotensin II Cardiovascular diseases Cardiac arrhythmias |
topic |
Renin-Angiotensin system Angiotensin II Cardiovascular diseases Cardiac arrhythmias Angiotensina II Fibrilación auricular Sistema Renina-Angiotensina Enfermedades cardiovasculares Arritmias cardiacas |
dc.subject.spa.fl_str_mv |
Angiotensina II Fibrilación auricular Sistema Renina-Angiotensina Enfermedades cardiovasculares Arritmias cardiacas |
publishDate |
2021 |
dc.date.accessioned.none.fl_str_mv |
2021-04-15 00:00:00 |
dc.date.available.none.fl_str_mv |
2021-04-15 00:00:00 |
dc.date.issued.none.fl_str_mv |
2021-04-15 |
dc.type.spa.fl_str_mv |
Artículo de revista |
dc.type.coar.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
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info:eu-repo/semantics/publishedVersion |
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http://purl.org/coar/resource_type/c_6501 |
dc.type.content.eng.fl_str_mv |
Text |
dc.type.driver.eng.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.local.eng.fl_str_mv |
Journal article |
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http://purl.org/coar/resource_type/c_6501 |
status_str |
publishedVersion |
dc.identifier.issn.none.fl_str_mv |
2215-7840 |
dc.identifier.doi.none.fl_str_mv |
10.32997/rcb-2021-3371 |
dc.identifier.eissn.none.fl_str_mv |
2389-7252 |
dc.identifier.url.none.fl_str_mv |
https://doi.org/10.32997/rcb-2021-3371 |
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2215-7840 10.32997/rcb-2021-3371 2389-7252 |
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https://doi.org/10.32997/rcb-2021-3371 |
dc.language.iso.eng.fl_str_mv |
eng |
language |
eng |
dc.relation.ispartofjournal.spa.fl_str_mv |
Revista Ciencias Biomédicas |
dc.relation.bitstream.none.fl_str_mv |
https://revistas.unicartagena.edu.co/index.php/cbiomedicas/article/download/3371/2857 |
dc.relation.citationedition.spa.fl_str_mv |
Núm. 2 , Año 2021 |
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119 |
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dc.relation.references.eng.fl_str_mv |
Zuljifly H, Lip G, Lane D. Epidemiology of atrial fibrillation. International Journal of Clinical Practice. 2018; 72(3): e13070. https://doi.org/10.1111/ijcp.13070 Shivshankar T, Lau D, Agbaedeng T, Elliott D, Mahajan R, Sanders P. Molecular mechanisms of atrial fibrosis: implications for the clinic. Expert Rev Cardiovasc Ther. 2017; 15(4): 247-256. https://doi.org/10.1080/14779072.2017.1299005 Lip GY, Tello-Montoliu A. Management of atrial fibrillation. Heart. 2006; 92(8): 1177-82. https://doi.org/10.1136/hrt.2005.071555 Lau DH, Middeldorp ME, Brooks AG, Ganesan AN, Roberts-Thomson KC, Stiles MK, et al. Aortic stiffness in lone atrial fibrillation: a novel risk factor for arrhythmia recurrence. PLoS One. 2013; 8(10): e76776. https://doi.org/10.1371/journal.pone.0076776 Pathak RK, Elliott A, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, et al. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study. J Am Coll Cardiol. 2015; 66(9): 985-96. https://doi.org/10.1016/j.jacc.2015.06.488 Tucker NR, Clauss S, Ellinor PT. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovasc Res. 2016; 109(4): 493-501. https://doi.org/10.1093/cvr/cvv283 Mascolo A, Urbanek K, De Angelis A, Sessa M, Scavone C, Berrino L, et al. Angiotensin II and angiotensin 1-7: which is their role in atrial fibrillation?. Heart Fail Rev. 2020; 25(2): 367-380. https://doi.org/10.1007/s10741-019-09837-7 Wagner P. Pathophysiology of hypertension: new concepts. Rev Peru Ginecol Obstet. 2018; 64(2): 175- 184. https://doi.org/10.31403/rpgo.v64i2075 Nehme A, Zouein FA, Zayeri ZD, Zibara K. An Update on the Tissue Renin Angiotensin System and Its Role in Physiology and Pathology. J Cardiovasc Dev Dis. 2019; 6(2): 14. https://doi.org/10.3390/jcdd6020014 Kishihara J, Niwano S, Niwano H, Aoyama Y, Ishikawa S, Oikawa J, et al. Long-term observation of fibrillation cycle length in patients under angiotensin II receptor blocker therapy for chronic atrial fibrillation. Journal of Arrhythmia. 2012; 28: 34-40. https://doi.org/10.1016/j.joa.2012.02.006 Fauchier L, de Groote P. Atrial fibrillation and renin- angiotensin-aldosterone system: believe it or not. Europace. 2011; 13(3): 297-8. https://doi.org/10.1093/europace/euq451 Arslan A, Ozaydin M, Aksoy F, Arslan B, Aydin H, Erdogan D, et al. Association between the use of renin- angiotensin system blockers and development of in- hospital atrial fibrillation in patients with ST-segment elevation myocardial infarction. Medicina. 2016; 52(2): 104-109. https://doi.org/10.1016/j.medici.2016.02.006 Seccia T, Caroccia B, Muiesan M, Rossi G. Atrial fibrillation and arterial hypertension: A common duet with dangerous consequences where the renin angiotensin-aldosterone system plays an important role. 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Available in: https://www.intechopen.com/books/atrial-fibrillation-mechanisms-and-treatment/atrial-fibrillation-and-the-renin-angiotensin-aldosterone-system ; https://doi.org/10.5772/53917 Youn J, Zhang J, Zhang Y, Chen H, Liu D, Ping P, et al. Oxidative stress in atrial fibrillation: an emerging role of NADPH oxidase. J Mol Cell Cardiol. 2013; 62: 72-79. https://doi.org/10.1016/j.yjmcc.2013.04.019 Lu G, Xu S, Peng L, Huang Z, Wang Y, Gao X. Angiotensin II upregulates Kv1.5 expression through ROS-dependent transforming growth factor-beta1 and extracellular signal-regulated kinase 1/2 signalings in neonatal rat atrial myocytes, Biochem Biophys Res Commun. 2014; 454(3): 410-416. https://doi.org/10.1016/j.bbrc.2014.10.088 Lu G, Xu C, Tang K, Zhang J, Li Q, Peng L. H2S inhibits angiotensin II-induced atrial Kv1.5 upregulation by attenuating Nox4/mediated EOS generation during atrial fibrillation. 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Circ Res. 2011; 108(2): 164- 75. https://doi.org/10.1161/CIRCRESAHA.110.234369 Ge Z, Chen Y, Wang B, Zhang X, Yan Y, Zhou L, et al. MFGE8 attenuates Ang-II-induced atrial fibrosis and vulnerability to atrial fibrillation through inhibition of TGF-β1/Smad2/3 pathway. J Mol Cell Cardiol. 2020; 139: 164-175. https://doi.org/10.1016/j.yjmcc.2020.01.001 Tsai CT, Lai LP, Kuo KT, Hwang JJ, Hsieh CS, Hsu KL, et al. Angiotensin II activates signal transducer and activators of transcription 3 via Rac1 in atrial myocytes and fibroblasts: implication for the therapeutic effect of statin in atrial structural remodeling. Circulation. 2008; 117(3): 344-55. https://doi.org/10.1161/CIRCULATIONAHA.107.695346 Zheng L, Jia X, Zhang C, Wang D, Cao Z, Wang J, et al. Angiotensin II in atrial structural remodeling: the role of Ang II/JAK/STAT3 signaling pathway. Am J Transl Res. 2015; 7(6): 1021-31. Tanaka Y, Obata K, Ohmori T, Ishiwata K, Abe M, Hamaguchi S, et al. Angiotensin II induces automatic activity of the isolated Guinea Pig pulmonary vein myocardium through activation of the IP3 receptor and the Na+-Ca2+ exchanger. Int J Mol Sci. 2019; 20(7): 1768. https://doi.org/10.3390/ijms20071768 Freedman B, Potpara TS, Lip GYH. Stroke prevention in atrial fibrillation. Lancet. 2016; 388(10046): 806-817. https://doi.org/10.1016/S0140-6736(16)31257-0 Fadhlullah AA, Abdalgbar AA, Altalhi HK. Non rheumatic atrial fibrillation as risk of stroke. Am J Internal Med. 2016; 4(6): 117. https://doi.org/10.11648/j.ajim.20160406.15 Ji C, Wu S, Shi J, Huang Z, Chen S, Wang G. Baseline CHADS2 score and risk of cardiovascular events in the population without atrial fibrillation. The American Journal of Cardiology. 2020; 129: 30-35. https://doi.org/10.1016/j.amjcard.2020.05.035 Saliba W, Gronich N, Barnett-Griness O, Rennert G. The role of CHADS2 and CHA2 DS2 -VASc scores in the prediction of stroke in individuals without atrial fibrillation: a population-based study. J Thromb Haemost. 2016; 14: 1155-1162. https://doi.org/10.1111/jth.13324 Lee D, Goldberger J, Fluckiger J, Ng J, Carr J, Collins J, et al. Analysis of left atrial flow velocity distribution by 4D flow MRI in patients with atrial fibrillation. Circulation. 2013; 128: A17900. Lee D, Markl M, Ng J, Carr M, Benefiled B, Carr J, et al. Atrial fibrillation is associated with altered left atrial 3D hemodynamics and increased stasis. Circulation. 2014; 130: A14026. https://doi.org/10.1161/circ.130.suppl_2.14026 Goldberger J, Fluckiger J, Lee D, Ng J, Olsen AB, Carr J, et al. Left atrial flow velocity distribution in atrial fibrillation by 4D flow MRI: A new marker for risk of stroke? Heart Rhythm. 2013; 10: S384. https://doi.org/10.1186/1532-429X-15-S1-P261 Siontis K, Geske J, Gersh B. Atrial fibrillation pathophysiology and prognosis insights from cardiovascular imaging. Circ Cardiovasc Imaging. 2015; 8(6): e003020. https://doi.org/10.1161/CIRCIMAGING.115.003020 Goldberger J, Arora R, Green D, Greenland P, Lee D, Lloyd D, et al. Evaluating the atrial myopathy underlying atrial fibrillation: identifying the arrhythmogenic and thrombogenic substrate. Circulation. 2015; 132(4): 278- 291. https://doi.org/10.1161/CIRCULATIONAHA.115.016795 Christersson C, Wallentin L, Andersson U, Alexander JH, Ansell J, De Caterina R, et al. D-dimer and risk of thromboembolic and bleeding events in patients with atrial fibrillation--observations from the ARISTOTLE trial. J Thromb Haemost. 2014; 12: 1401-1412. https://doi.org/10.1111/jth.12638 Claxton J, Chamberlain A, Lutsey P, Chen L, MacLehose R, Bengston L, et al. Association of multimorbidity with cardiovascular endpoints and treatment effectiveness in patients 75 years and older with atrial fibrillation. The American Journal of Medicine. 2020; 133(10): e554-e567. https://doi.org/10.1016/j.amjmed.2020.03.038 Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH, et al. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE- LY) substudy. Circulation. 2012; 125:1605-1616. https://doi.org/10.1161/CIRCULATIONAHA.111.038729 Rubattu S, Volpe M. Natriuretic peptides in the cardiovascular system: multifaceted roles in physiology, pathology and therapeutics. Int J Mol Sci. 2019; 20(16):3991. https://doi.org/10.3390/ijms20163991 Patton KK, Heckbert SR, Alonso A, Bahrami H, Lima JA, Burke G, et al. N-terminal pro-B-type natriuretic peptide as a predictor of incident atrial fibrillation in the Multi-Ethnic Study of Atherosclerosis: The effects of age, sex and ethnicity. Heart. 2013; 99: 1832-1836. https://doi.org/10.1136/heartjnl-2013-304724 Svennberg E, Lindahl B, Berglund L, Eggers KM, Venge P, Zethelius B, et al. NT-proBNP is a powerful predictor for incident atrial fibrillation-Validation of a multimarker approach. Int J Cardiol. 2016; 223: 74-81. https://doi.org/10.1016/j.ijcard.2016.08.001 Sinner MF, Stepas KA, Moser CB, Krijthe BP, Aspelund T, Sotoodehnia N, et al. B-type natriuretic peptide and C- reactive protein in the prediction of atrial fibrillation risk: The CHARGE-AF Consortium of community-based cohort studies. Europace. 2014; 16: 1426-1433. https://doi.org/10.1093/europace/euu175 Schnabel RB, Larson MG, Yamamoto JF, Sullivan LM, Pencina MJ, Meigs JB, et al. Relations of biomarkers of distinct pathophysiological pathways and atrial fibrillation incidence in the community. 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Circulation. 1999; 100(4): 376-80. https://doi.org/10.1161/01.CIR.100.4.376 Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular disease (TRANSCEND) Investigators, Yusuf S, Teo K, Anderson C, Pogue J, Dyal L, Copland I, et al. Effects of the angiotensin-receptor blocker telmisartan on cardiovascular events in high-risk patients intolerant to angiotensin-converting enzyme inhibitors: a randomised controlled trial. Lancet. 2008; 372(9644): 1174-83. https://doi.org/10.1016/S0140-6736(08)61242-8 Dahl JS, Videbaek L, Poulsen MK, Pellikka PA, Veien K, Andersen LI, et al. Effect of candesartan treatment on left ventricular remodeling after aortic valve replacement for aortic stenosis. Am J Cardiol. 2010; 106(5): 713-9. https://doi.org/10.1016/j.amjcard.2010.04.028 Swedberg K, Zannad F, McMurray JJ, Krum H, van Veldhuisen DJ, Shi H, et al. Eplerenone and atrial fibrillation in mild systolic heart failure: results from the EMPHASIS-HF (Eplerenone in Mild Patients Hospitalization and SurvIval Study in Heart Failure) study. J Am Coll Cardiol. 2012; 59(18): 1598-603. https://doi.org/10.1016/j.jacc.2011.11.063 Khatib R, Joseph P, Briel M, Yusuf S, Healey J. Blockade of the renin-angiotensin-aldosterone system (RAAS) for primary prevention of non-valvular atrial fibrillation: a systematic review and meta analysis of randomized controlled trials. Int J Cardiol. 2013; 165(1): 17-24. https://doi.org/10.1016/j.ijcard.2012.02.009 Carson JA, Turner AJ. Beta-amyloid catabolism: Roles for neprilysin (nep) and other metallopeptidases?. J Neurochem. 2002; 81: 1-8. https://doi.org/10.1046/j.1471-4159.2002.00855.x Barnes K, Turner AJ, Kenny AJ. Membrane localization of endopeptidase-24.11 and peptidyl dipeptidase a (angiotensin converting enzyme) in the pig brain: A study using subcellular fractionation and electron microscopic immunocytochemistry. J Neurochem. 1992; 58: 2088- 2096. https://doi.org/10.1111/j.1471-4159.1992.tb10950.x Stephenson SL, Kenny AJ. Metabolism of neuropeptides. Hydrolysis of the angiotensins, bradykinin, substance p and oxytocin by pig kidney microvillar membranes. Biochem J. 1987; 241: 237-247. https://doi.org/10.1042/bj2410237 McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, et al. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014; 371(11): 993-1004. https://doi.org/10.1056/NEJMoa1409077 Solomon S, Rizkala A, Gong J, Wang W, Anand I, Ge J, et al. Angiotensin receptor neprilisyn inhibition in heart failure with preserved ejection fraction: Rationale and design of the PARAGON-HF Trial. JACC Heart Fail. 2017; 5(7): 471-482. https://doi.org/10.1016/j.jchf.2017.04.013 Okutucu S, Fatihoglu SG, Sabanoglu C, Bursa N, Sayin BY, Aksoy H, et al. Effects of angiotensin receptor neprilysin inhibition on P-wave dispersion in heart failure with reduced ejection fraction. Herz. 2019. https://doi.org/10.1007/s00059-019-04872-4 Desai AS, McMurray JJ, Packer M, Swedberg K, Rouleau JL, Chen F, et al. Effect of the angiotensin- receptor-neprilysin inhibitor LCZ696 compared with enalapril on mode of death in heart failure patients. Eur Heart J. 2015; 36(30): 1990-1997. https://doi.org/10.1093/eurheartj/ehv186 De Diego C, Gonzalez-Torres L, Nunez JM, Centurion Inda R, Martin-Langerwerf DA, Sangio AD, et al. Effects of angiotensin-neprilysin inhibition compared to angiotensin inhibition on ventricular arrhythmias in reduced ejection fraction patients under continuous remote monitoring of implantable defibrillator devices. Heart Rhytm. 2018; 15(3): 395-402. https://doi.org/10.1016/j.hrthm.2017.11.012 Song S, Zhang R, Mo B, Chen L, Liu L, Yu Y, et al. EZH2 as a novel therapeutic target for atrial fibrosis and atrial fibrillation. J Mol Cell Cardiol. 2019; 135: 119-133. https://doi.org/10.1016/j.yjmcc.2019.08.003 |
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Llamas Nieves, Andrés ElíasLozada Martínez, Ivan DavidTorres Llinás, Daniela MarcelaManzur Jattin, FernandoCardales Periñán, Miguel2021-04-15 00:00:002021-04-15 00:00:002021-04-152215-784010.32997/rcb-2021-33712389-7252https://doi.org/10.32997/rcb-2021-3371application/pdfengUniversidad de CartagenaRevista Ciencias Biomédicashttps://revistas.unicartagena.edu.co/index.php/cbiomedicas/article/download/3371/2857Núm. 2 , Año 2021119210910Zuljifly H, Lip G, Lane D. Epidemiology of atrial fibrillation. International Journal of Clinical Practice. 2018; 72(3): e13070. https://doi.org/10.1111/ijcp.13070Shivshankar T, Lau D, Agbaedeng T, Elliott D, Mahajan R, Sanders P. Molecular mechanisms of atrial fibrosis: implications for the clinic. Expert Rev Cardiovasc Ther. 2017; 15(4): 247-256. https://doi.org/10.1080/14779072.2017.1299005Lip GY, Tello-Montoliu A. Management of atrial fibrillation. Heart. 2006; 92(8): 1177-82. https://doi.org/10.1136/hrt.2005.071555Lau DH, Middeldorp ME, Brooks AG, Ganesan AN, Roberts-Thomson KC, Stiles MK, et al. Aortic stiffness in lone atrial fibrillation: a novel risk factor for arrhythmia recurrence. PLoS One. 2013; 8(10): e76776. https://doi.org/10.1371/journal.pone.0076776Pathak RK, Elliott A, Middeldorp ME, Meredith M, Mehta AB, Mahajan R, et al. Impact of CARDIOrespiratory FITness on Arrhythmia Recurrence in Obese Individuals With Atrial Fibrillation: The CARDIO-FIT Study. J Am Coll Cardiol. 2015; 66(9): 985-96. https://doi.org/10.1016/j.jacc.2015.06.488Tucker NR, Clauss S, Ellinor PT. Common variation in atrial fibrillation: navigating the path from genetic association to mechanism. Cardiovasc Res. 2016; 109(4): 493-501. https://doi.org/10.1093/cvr/cvv283Mascolo A, Urbanek K, De Angelis A, Sessa M, Scavone C, Berrino L, et al. Angiotensin II and angiotensin 1-7: which is their role in atrial fibrillation?. 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J Mol Cell Cardiol. 2019; 135: 119-133. https://doi.org/10.1016/j.yjmcc.2019.08.003Andrés Elías Llamas Nieves - 2021https://creativecommons.org/licenses/by-nc-sa/4.0http://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessEsta obra está bajo una licencia internacional Creative Commons Atribución-NoComercial-CompartirIgual 4.0.https://revistas.unicartagena.edu.co/index.php/cbiomedicas/article/view/3371Renin-Angiotensin systemAngiotensin IICardiovascular diseasesCardiac arrhythmiasAngiotensina IIFibrilación auricularSistema Renina-AngiotensinaEnfermedades cardiovascularesArritmias cardiacasNovedades sobre angiotensina II y fibrilación auricular : de lo molecular a lo fisiopatológico.News on angiotensin II and atrial fibrillation : from the molecular to the pathophysiological.Artículo de revistainfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/version/c_970fb48d4fbd8a85http://purl.org/coar/resource_type/c_6501http://purl.org/coar/resource_type/c_2df8fbb1Textinfo:eu-repo/semantics/articleJournal articlePublicationOREORE.xmltext/xml2568https://repositorio.unicartagena.edu.co/bitstreams/a7a9323c-6040-48e2-8b49-ac234f612474/download369c2e42b72cdd79e7147da240d1e9b5MD5111227/13457oai:repositorio.unicartagena.edu.co:11227/134572024-09-05 15:30:42.675https://creativecommons.org/licenses/by-nc-sa/4.0Andrés Elías Llamas Nieves - 2021metadata.onlyhttps://repositorio.unicartagena.edu.coBiblioteca Digital Universidad de Cartagenabdigital@metabiblioteca.com |