Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats
Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeu...
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Frontiers Media S.A.
2021-01-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2020.600953/full |
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| author | Wenchao Zhang Wenchao Zhang Jianwei Liu Yang Fu Huifang Ji Zheyan Fang Wanming Zhou Huimin Fan Yingxuan Zhang Yan Liao Ting Yang Xiaolin Wang Wanwan Yuan Xiaoshu Chen Yi-fei Dong |
| author_facet | Wenchao Zhang Wenchao Zhang Jianwei Liu Yang Fu Huifang Ji Zheyan Fang Wanming Zhou Huimin Fan Yingxuan Zhang Yan Liao Ting Yang Xiaolin Wang Wanwan Yuan Xiaoshu Chen Yi-fei Dong |
| author_sort | Wenchao Zhang |
| collection | DOAJ |
| description | Previous studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF. |
| first_indexed | 2024-12-24T05:10:52Z |
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| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-24T05:10:52Z |
| publishDate | 2021-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-136ae76ce28442ef9cc591044ba7549a2022-12-21T17:13:41ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-01-011110.3389/fphar.2020.600953600953Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in RatsWenchao Zhang0Wenchao Zhang1Jianwei Liu2Yang Fu3Huifang Ji4Zheyan Fang5Wanming Zhou6Huimin Fan7Yingxuan Zhang8Yan Liao9Ting Yang10Xiaolin Wang11Wanwan Yuan12Xiaoshu Chen13Yi-fei Dong14Department of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaChang Xing People’s Hospital, Huzhou, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaDepartment of Cardiovascular Medicine, the Second Affiliated Hospital of Nanchang University, Nanchang, ChinaPrevious studies have confirmed the clinical efficacy of sacubitril/valsartan (Sac/Val) for the treatment of heart failure with reduced ejection fraction (HFrEF). However, the role of Sac/Val in heart failure with preserved ejection fraction (HFpEF) remains unclear. Sac/Val is a combination therapeutic medicine comprising sacubitril and valsartan that acts as a first angiotensin receptor blocker and neprilysin inhibitor (angiotensin-receptor neprilysin inhibitor (ARNI)). Here, we investigated the role of Sac/Val in high-salt diet-induced HFpEF coupled with vascular injury as well as the underlying mechanism. Rats were fed with high-salt feed, followed by intragastric administration of Sac/Val (68 mg/kg; i.g.). The results of functional tests revealed that a high-salt diet caused pathological injuries in the heart and vascular endothelium, which were significantly reversed by treatment with Sac/Val. Moreover, Sac/Val significantly decreased the levels of fibrotic factors, including type I collagen and type Ⅲ collagen, thus, reducing the ratio of MMP2/TIMP2 while increasing Smad7 levels. Further investigation suggested that Sac/Val probably reversed the effects of high-salt diet-induced HFpEF by inhibiting the activation of the TGF-β1/Smad3 signaling pathway. Thus, treatment with Sac/Val effectively alleviated the symptoms of high-salt diet-induced HFpEF, probably by inhibiting fibrosis via the TGF-β1/Smad3 signaling pathway, supporting the therapeutic potential of Sac/Val for the treatment of HFpEF.https://www.frontiersin.org/articles/10.3389/fphar.2020.600953/fullheart failure with preserved ejection fractionvascular injurysacubitril/valsartanfibrosishigh-salt diet |
| spellingShingle | Wenchao Zhang Wenchao Zhang Jianwei Liu Yang Fu Huifang Ji Zheyan Fang Wanming Zhou Huimin Fan Yingxuan Zhang Yan Liao Ting Yang Xiaolin Wang Wanwan Yuan Xiaoshu Chen Yi-fei Dong Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats Frontiers in Pharmacology heart failure with preserved ejection fraction vascular injury sacubitril/valsartan fibrosis high-salt diet |
| title | Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats |
| title_full | Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats |
| title_fullStr | Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats |
| title_full_unstemmed | Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats |
| title_short | Sacubitril/Valsartan Reduces Fibrosis and Alleviates High-Salt Diet-Induced HFpEF in Rats |
| title_sort | sacubitril valsartan reduces fibrosis and alleviates high salt diet induced hfpef in rats |
| topic | heart failure with preserved ejection fraction vascular injury sacubitril/valsartan fibrosis high-salt diet |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2020.600953/full |
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