The role of sacubitril valsartan in experimental animal models

Öz

The benefits of sacubutril/valsartan (S/V), a new molecule in the treatment of heart failure, have been demonstrated in large and comprehensive studies and have been put into use in daily practice. This drug combination was developed to counteract the detrimental effects of renin-angiotensin-aldosterone system (RAAS) activation while increasing levels of potentially beneficial endogenous vasoactive peptides degraded by neprilysin. In the last 2022 European Society of Cardiology Heart Failure Guidelines, there is a class 1 indication with ACE-Is and beta blockers, which had a treat-ment class 1 indication previously published in heart failure. In addition, the effects of S/V were examined in different experimental animal models, so etiological differences were also evaluated and continue to be evaluated. In this review, we aimed to summarize experimental animal studies with S/V.

Anahtar Kelimeler

• Sacubutril/Valsartan
• Heart Failure
• Animal
• Experimental

Proje Numarası

Proje numarası: TTU-2019-2907

Sakubitril valsartan’ın deneysel havyan modellerindeki yeri

Öz

Kalp yetersizliği tedavisinde yeni bir molekül olan sakubutril/valsartan’ın (S/V) büyük ve kapsamlı çalışmalarda faydaları ortaya koyulmuş ve günlük pratikte kullanıma sunulmuştur. Bu ilaç kombinasyonu, neprilisin tarafından bozulan potansiyel olarak faydalı endojen vazoaktif peptitlerin seviyelerini arttırırken, renin anjiyotensin aldosteron sistemi (RAAS) aktivasyonunun zararlı etkilerini engellemek için geliştirilmiştir. Son yayınlanan 2022 Avrupa Kardiyoloji Derneği Kalp Yetersizliği Kılavuzu’nda da daha önce kalp yetersizliği tedavisinde sınıf 1 endikasyona sahip olan ACE-İ ve beta blokerler ile birlikte sınıf 1 endikasyonu almıştır. Bunun yanında farklı deneysel hayvan modellerinde de S/V’ın etkileri incelenmiş, böylece etiyolojik farklılıklar da değerlendirilmiş ve incelenmeye, değerlendirilmeye devam etmektedir. Bu derlemede S/V ile yapılmış deneysel hayvan çalışmalarını özetlemeyi amaçladık.

Anahtar Kelimeler

• Sacubutril/Valsartan
• Kalp yetersizliği
• Hayvan
• Deneysel

Destekleyen Kurum

Bu derleme Çanakkale Onsekiz Mart Üniversitesi Bilimsel Araştırma Projesi tarafından desteklenen tez çalışmasından üretilmiştir.

Proje Numarası

Proje numarası: TTU-2019-2907

Teşekkür

Desteklerinden dolayı Çanakkale Onsekiz Mart Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi'ne teşekkür ederiz.

Kaynakça

1. 1- Voors AA, Dorhout B, MeerP. The potential role of valsartan+AHU377 (LCZ696) in the treatment of heart failure. Expert opin investig drugs 2013;22(8):1041–7.
2. 2- Gu J, Noe A, Chandra P, et al. Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angio-tensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol 2010;50(4): 401–14
3. 3-Abboud A, Januzzi JL. Reverse cardiac remodeling and ARNI therapy. Curr Heart Fail Rep. 2021;18(2):71-83.
4. 4-Cho IJ, Kang SM. Angiotensin receptor-neprilysin inhibitor in patients with heart failure and chronic kidney disease. Kidney Res Clin Pract. 2021;40(4):555-65.
5. 5-Dong Y, Xu Y, et al. Comparing the efficacy of angiotensin receptor-neprilysin inhibitor and enalapril in acute anterior STEMI patients after primary percutaneous coronary intervention: a prospective randomized trial. Cardiovasc Diagn Ther. 2022;12(1):42-54.
6. 6- Gardner DG, Chen S, Glenn DJ, Grigsby CL. Molecular biology of the natriuretic peptide system: implications for physiology and hypertension. Hypertension 2007;49(3):419–26
7. 7- McMurray JV, Packer M, Desai AS, et al. Angiotensin–neprilysin inhibition versus enalapril in heart failure. N Engl J Med 2014;371(11):993-1004.
8. 8- King JB, Bress AP, Reese AD, Munger MA. Neprilysin inhibition in heart failure with reduced ejection fraction: a clinical review. Pharmacotherapy 2015;35(9):823–37.

9. 9- McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021 Sep 21;42(36):3599-726.
10. 10- Solomon SD, McMurray JJV, Anand IS, et al. Angio-tensin–neprilysin inhibition in heart failure with preserved ejection fraction. N Engl J Med 2019; 381(17):1609-20.
11. 11- Solomon SD, Zile M, Pieske B, et al. Prospective comparison of ARNI with ARB on management of heart failure with preserved ejection fracTion (PARAMOUNT) investigators. The angiotensin receptor neprilysin inhibitor LCZ696 in heart failure with preserved ejection fraction: a phase 2 double-blind randomised controlled trial. Lancet 2012;380(9851):1387–95
12. 12- Wu M, Guo Y, Wu Y, Xu K, Lin L. Protective effects of sacubitril/valsartan on cardiac fibrosis and function in rats with experimental myocardial infarction involves .nhibition of collagen synthesis by myocardial fibroblasts through downregulating TGF-β1/Smads pathway. Front Pharmacol 2021 May 31;12:696472.
13. 13- Li X, Braza J, Mende U, et al. Cardioprotective effects of early intervention with sacubitril/valsartan on pressure overloaded rat hearts. Sci Rep. 2021;11(1):16542.
14. 14- Croteau D, Qin F, Chambers JM, et al. Differential effects of sacubitril/valsartan on diastolic function in mice with obesity-related metabolic heart disease. JACC: Basic to Translational Science 2020;5(9):916–27
15. 15- Miyoshi T, Nakamura K, Miura D, et al. Effect of LCZ696, a dual angiotensin receptor neprilysin inhibitor, on isoproterenol-induced cardiac hypertrophy, fibrosis, and hemodynamic change in rats. Cardiol J. 2019;26(5):575–83
16. 16- Suematsu Y, Miura S, Goto M, et al. LCZ696, an angiotensin receptor-neprilysin inhibitor, improves cardiac function with the attenuation of fibrosis in heart failure with reduced ejection fraction in streptozotocin-induced diabetic mice. Eur J Heart Fail. 2016;18(4):386-93.
17. 17- Boutagy NE, Feher A, Pfau D, et al. Dual Angiotensin receptor-neprilysin inhibition with sacubitril/valsartan attenuates systolic dysfunction in experimental doxorubicin-Induced cardiotoxicity. JACC: CardioOncol. 2020;2(5):774–87.
18. 18- Suo Y, Yuan M, Li H, et al. Sacubitril/valsartan improves left atrial and left atrial appendage function in patients with atrial fibrillation and in pressure overload-induced mice. Front Pharmacol. 2019 Oct 29;10:1285.
19. 19- Li LY, Lou Q, Liu GZ, et al. Sacubitril/valsartan attenuates atrial electrical and structural remodelling in a rabbit model of atrial fibrillation. . Eur J Pharmacol. 2020 Aug 15;881:173120.
20. 20- Sharifi Kia D, Benza E, Bachman TN, et al. Angiotensin receptor‐neprilysin inhibition attenuates right ventricular remodeling in pulmonary hypertension. J Am Heart Assoc 2020;9(13): e015708.
21. 21- Ishii M, Kaikita K, Sato K, et al. Cardioprotective effects of LCZ696 (sacubitril/valsartan) after experimental acute myocardial infarction. JACC Basic Transl Sci. 2017;2(6):655-68
22. 22- Shen J, Fan Z, Sun G, Qi G. Sacubitril/valsartan (LCZ696) reduces myocardial injury following myocardial infarction by inhibiting NLRP3 induced pyroptosis via the TAK1/JNK signaling pathway. Mol Med Rep 2021;24(3): 676.
23. 23- Godsel LM, Leon JS, Wang K, et al. Captopril prevents experimental autoimmune myocarditis. J Immunol 2003;171(1):346-52.
24. 24-Xuefei Liu, Xinglei Zhu, Wang A et al. Effects of angiotensin-II receptor blockers on experimental autoimmune myocarditis. Int J Cardiol 2009;137(3):282-88.
25. 25- Sukumaran V, Veeraveedu PT, Gurusamy N, et al. Cardioprotective effects of telmisartan against heart failure in rats induced by experimental autoimmune myocarditis through the modulation of angiotensin-converting enzyme-2/angiotensin 1-7/mas receptor axis. Int J Biol Sci 2011;7(8):1077-92.
26. 26- Atteya M, Mohamed RA, Ahmed AM, et al. Lisinopril has a cardio-protective effect on experimental acute auto-immune myocarditis in rats. Histol Histopathol 2017;32(4):405-12.
27. 27- Duygu A, Gazi E, Deveci B, Arslan M, Oztopuz R, Adali Y. Could ARNI have an effect on LV fibrosis and inflammatory parameters in an experimental autoimmune myocarditis model?. Eurasian Journal Medical Investigation 2022;6(2)