medigraphic.com
ISSN 2954-3835 (Digital)
ISSN 2683-2828 (Impreso)

2026, Número 2

<< Anterior Siguiente >>

Cardiovasc Metab Sci 2026; 37 (2)


Evaluación comparativa de sacubitril-valsartán y nebivolol-valsartán en la remodelación ventricular izquierda tras un infarto de miocardio crónico en ratas Wistar hembras

Pérez-García E, Valencia-Hernández I, Lezama-Martínez D, Ramírez-Hernández D, Garrido-Fariña GI, Ramírez-Hernández C, Reyes-Alvarado K, Hidalgo I, Flores-Monroy J

Idioma: Inglés [English version]
Referencias bibliográficas: 34
Paginas: 60-73
Archivo PDF: 2885.10 Kb.


RESUMEN

La fibrosis cardiaca tras un infarto de miocardio (IM) provoca una remodelación ventricular izquierda adversa e insuficiencia cardiaca, observándose patrones distintos en las mujeres. A pesar de presentar infartos de menor tamaño y una menor actividad profibrótica, las mujeres tienen un mayor riesgo de mortalidad tras un IM y de insuficiencia cardiaca. Dado que las terapias actuales se dirigen directamente a la fibrosis, el estudio de estos mecanismos es esencial para desarrollar y evaluar tratamientos, incluidos los fármacos aprobados para la insuficiencia cardiaca, como el sacubitril-valsartán. El objetivo de este estudio fue comparar y evaluar la combinación de nebivolol-valsartán (NV) frente a sacubitril-valsartán (SV) como tratamiento conocido para el infarto crónico en ratas hembras. Se utilizaron ratas Wistar de 26 semanas de edad. Los animales se dividieron en cuatro grupos (n = 6): 1) control (SHAM); 2) infarto de miocardio (LADL); 3) LADL + sacubitril 30 mg/kg/día + valsartán 28 mg/kg/día (LADL + SV); 4) LADL + valsartán 30 mg/kg/día + nebivolol 5 mg/kg/día (LADL + NV). La inducción del infarto se realizó mediante ligadura permanente de la arteria coronaria descendente anterior izquierda. Los grupos tratados recibieron sus tratamientos inmediatamente después de la inducción del infarto durante dos semanas. Las ratas fueron sacrificadas mediante dislocación cervical y se extrajeron los corazones y los pulmones de todos los grupos para su análisis histológico mediante tinción de Van Gieson y HE. La combinación de resulted in six experimental groups. There was a reduction in the mortality rate, reduction of hypertrophy and cardiac fibrosis when the NV combination was administered seven days after ligation. In conclusion, sacubitril–valsartan appears to be a safe and effective strategy to attenuate cardiac and pulmonary fibrosis after infarction female rats, however, based on the results, early administration of nebivololvalsartan is not recommended, as it appears to increase the risk of post-infarction complications.


REFERENCIAS (EN ESTE ARTÍCULO)

  1. Martin SS, Aday AW, Allen NB, Almarzooq ZI,Anderson CAM, Arora P et al. Correction to: 2025Heart disease and stroke statistics: a report of US andglobal data from the American Heart Association.Circulation. 2025; 151 (25): e1096.

  2. Holtzman JN, Kaur G, Power JE, Barkhordarian M,Mares A, Goyal A et al. Underrepresentation of womenin late-breaking cardiovascular clinical trials. J WomensHealth (Larchmt). 2023; 32 (6): 635-640.

  3. Prabhu SD, Frangogiannis NG. The biological basisfor cardiac repair after myocardial infarction: frominflammation to fibrosis. Circ Res. 2016; 119 (1):91-112.

  4. Talman V, Ruskoaho H. Cardiac fibrosis in myocardialinfarction-from repair and remodeling to regeneration.Cell Tissue Res. 2016; 365 (3): 563-581.

  5. Frangogiannis NG. Cardiac fibrosis. Cardiovasc Res.2021; 117 (6): 1450-1488.

  6. Ravassa S, López B, Treibel TA, San José G, Losada-Fuentenebro B, Tapia L et al. Cardiac fibrosis in heartfailure: focus on non-invasive diagnosis and emergingtherapeutic strategies. Mol Aspects Med. 2023; 93:101194.

  7. Gissler MC, Antiochos P, Ge Y, Heydari B, Grani C,Kwong RY. Cardiac magnetic resonance evaluation ofLV remodeling post-myocardial infarction: prognosis,monitoring and trial endpoints. JACC CardiovascImaging. 2024; 17 (11): 1366-1380.

  8. Aimo A, Panichella G, Barison A, Maffei S, Cameli M,Coiro S et al. Sex-related differences in ventricularremodeling after myocardial infarction. Int J Cardiol.2021; 339: 62-69.

  9. Dekleva M, Djordjevic A, Zivkovic S, Lazic JS.Specificities of myocardial infarction and heart failurein women. J Clin Med. 2024; 13 (23): 7319.

  10. Platz E, Merz AA, Jhund PS, Vazir A, Campbell R,McMurray JJ. Dynamic changes and prognostic valueof pulmonary congestion by lung ultrasound in acuteand chronic heart failure: a systematic review. Eur JHeart Fail. 2017; 19 (9): 1154-1163.

  11. Zannad F, Ferreira JP. Is sacubitril/valsartan antifibrotic?J Am Coll Cardiol. 2019; 73 (7): 807-809.

  12. Shi YJ, Yang CG, Qiao WB, Liu YC, Liu SY, DongGJ. Sacubitril/valsartan attenuates myocardialinflammation, hypertrophy, and fibrosis in rats withheart failure with preserved ejection fraction. Eur JPharmacol. 2023; 961: 176170.

  13. Varagic J, Ahmad S, Voncannon JL, Moniwa N,Simington SW, Brosnihan BK et al. Nebivolol reducescardiac angiotensin II, associated oxidative stressand fibrosis but not arterial pressure in salt-loadedspontaneously hypertensive rats. J Hypertens. 2012;30 (9): 1766-1774.

  14. Rajendran A, Minhas AS, Kazzi B, Varma B, ChoiE, Thakkar A et al. Sex-specific differences incardiovascular risk factors and implications forcardiovascular disease prevention in women.Atherosclerosis. 2023; 384: 117269.

  15. Medzikovic L, Aryan L, Eghbali M. Connecting sexdifferences, estrogen signaling, and microRNAs incardiac fibrosis. J Mol Med (Berl). 2019; 97 (10):1385-1398.

  16. Ramírez-Hernández D, López-Sanchez P, Rosales-Hernández MC, Fonseca-Coronado S, Flores-MonroyJ. Estrous cycle phase affects myocardial infarctionthrough reactive oxygen species and nitric oxide. FrontBiosci (Landmark Ed). 2021; 26 (12): 1434-1443.

  17. DiLorenzo MP, Grosse-Wortmann L. Myocardialfibrosis in congenital heart disease and the role of MRI.Radiol Cardiothorac Imaging. 2023; 5 (3): e220255.

  18. Valentin J, Frobert A, Ajalbert G, Cook S, Giraud MN.Histological quantification of chronic myocardialinfarct in rats. J Vis Exp. 2016; 118: 54914.

  19. Pfeffer MA, Pfeffer JM, Steinberg C, Finn P. Survivalafter an experimental myocardial infarction: beneficialeffects of long-term therapy with captopril. Circulation.1985; 72 (2): 406-412.

  20. Puymirat E, Riant E, Aissaoui N, Soria A, Ducrocq G,Coste P et al. β blockers and mortality after myocardialinfarction in patients without heart failure: multicentreprospective cohort study. BMJ. 2016; 354: i4801.

  21. Xia QG, Chung O, Spitznagel H, Illner S, Janichen G,Rossius B et al. Significance of timing of angiotensinAT1 receptor blockade in rats with myocardialinfarction-induced heart failure. Cardiovasc Res. 2001;49 (1): 110-117.

  22. Liu Y, Zhong C, Si J, Chen S, Kang L, Xu B. The impactof Sacubitril/Valsartan on cardiac fibrosis early aftermyocardial infarction in hypertensive rats. J Hypertens.2022; 40 (9): 1822-1830.

  23. Torrado J, Cain C, Mauro AG, Romeo F, Ockaili R,Chau VQ et al. Sacubitril/valsartan averts adversepost-infarction ventricular remodeling and preservessystolic function in rabbits. J Am Coll Cardiol. 2018;72 (19): 2342-2356.

  24. Gabriel-Costa D. The pathophysiology of myocardialinfarction-induced heart failure. Pathophysiology.2018; 25 (4): 277-284.

  25. Xiao F, Wang L, Liu M, Chen M, He H, Jia Z et al.Sacubitril/valsartan attenuates myocardial ischemia/reperfusion injury via inhibition of the GSK3β/NF-κBpathway in cardiomyocytes. Arch Biochem Biophys.2022; 730: 109415.

  26. Sui X, Wei H, Wang D. Novel mechanism of cardiacprotection by valsartan: synergetic roles of TGF-β1 andHIF-1α in Ang II-mediated fibrosis after myocardialinfarction. J Cell Mol Med. 2015; 19 (8): 1773-1782.

  27. Zhang Z, Ding L, Jin Z, Gao G, Li H, Zhang L et al.Nebivolol protects against myocardial infarction injuryvia stimulation of beta 3-adrenergic receptors and nitricoxide signaling. PLoS One. 2014; 9 (5): e98179.

  28. Leask A. Potential therapeutic targets for cardiacfibrosis: TGFbeta, angiotensin, endothelin, CCN2, andPDGF, partners in fibroblast activation. Circ Res. 2010;106 (11): 1675-1680.

  29. Vaskova E, Ikeda G, Tada Y, Wahlquist C, Mercola M,Yang PC. Sacubitril/valsartan improves cardiac functionand decreases myocardial fibrosis via downregulationof exosomal miR-181a in a rodent chronic myocardialinfarction model. J Am Heart Assoc. 2020; 9 (13):e015640.

  30. Burke RM, Lighthouse JK, Mickelsen DM, Small EM.Sacubitril/valsartan decreases cardiac fibrosis in leftventricle pressure overload by restoring PKG signalingin cardiac fibroblasts. Circ Heart Fail. 2019; 12 (4):e005565.

  31. Chen Y, Guo H, Xu D, Xu X, Wang H, Hu X et al. Leftventricular failure produces profound lung remodelingand pulmonary hypertension in mice: heart failurecauses severe lung disease. Hypertension. 2012; 59(6): 1170-1178.

  32. Perros F, Ranchoux B, Izikki M, Bentebbal S, HappéC, Antigny F et al. Nebivolol for improving endothelialdysfunction, pulmonary vascular remodeling, and rightheart function in pulmonary hypertension. J Am CollCardiol. 2015; 65 (7): 668-680.

  33. Zhou M, Meng L, He Q, Ren C, Li C. Valsartanattenuates LPS-induced ALI by modulating NF-κBand MAPK pathways. Front Pharmacol. 2024; 15:1321095.

  34. Jin HK, Yang RH, Thornton RM, Chen YF, JacksonR, Oparil S. Atrial natriuretic peptide lowerspulmonary arterial pressure in hypoxia-adaptedrats. J Appl Physiol (1985). 1988; 65 (4): 1729-1735.




2020     |     www.medigraphic.com