TABLE 5.

The effects of sacubitril/valsartan on myocardial fibrosis in animal studies.

Type of model	Treatment, dose, route of administration and duration	Findings	References
Left anterior descending ligation-induced MI in rats	Post-treatment 60 mg/kg/day, orally for 4 weeks (1 week after surgery)	↓ cardiac fibrosis, ↓ collagen I, ↓ TIMP-2	Kompa et al. (2018)
Isoproterenol-induced cardiac hypertrophy	Concurrent treatment 60 mg/kg/day, orally for 7 days	↓ interstitial fibrosis area, ↓TGFβ1, ↓ collagen 1a1	Miyoshi et al. (2019)
Spontaneously hypertensive rats	60 mg/kg/day for 12 weeks	↓ nNos, ↓ eNos, ↓ TGF-β, ↓ RAS components	Zhao et al. (2019)
Aortic valve insufficiency (AVI)-induced HF in rats	Post-treatment 68 mg/kg/day, orally for 8 weeks	↓ myocardial fibrosis	Maslov et al. (2019a)
Spontaneous hypertensive rats	300 mg/kg, orally for 2 weeks	↓ fibrosis area	Sung et al. (2020)
Pulmonary hypertension-induced RV failure in rats	Post-treatment 60 mg/kg/day for 5 weeks	↓ fibrosis volume density, ↓ total fibrosis volume	Andersen et al. (2019)
Obesity-associated diastolic dysfunction in Zucker obese rats	68 mg/kg/day, orally for 10 weeks	↓ LV myocardial interstitial fibrosis, ↓ LV periarterial fibrosis	Aroor et al. (2021)
Ligated-induced MI in rats	Post-treatment 60 mg/kg, orally for 4 weeks	↓ fibrotic area, ↓ α-SMA level and area, ↓ TGF-β mRNA level	Liu et al. (2021b)

eNOS, endothelial nitric oxide synthase; LV, left ventricle; MI, myocardial infarction; nNOS, neuronal nitric oxide synthase; RAS, renin-angiotensin system; TIMP, tissue inhibitor of matrix metalloproteinase; α-SMA, highly contractile protein α-smooth muscle actin; TGFβ1, transforming growth factor β1; ↓, decrease; ↑, increase; ↔, no effect.