Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis

Shen, Jianfen; Fan, Zhongbao; Wu, Chun-Wei; Qi, Guoxian; Cao, Qiu-Yu; Xu, Feng

doi:10.1155/2022/5009289

Cited by 5 publications

(3 citation statements)

References 38 publications

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“…S/V effectively ameliorates symptoms in patients with chronic HF and AMI ( 6 , 7 , 26 ). In rats, S/V results in a marked improvement in cardiac function and reductions in oxidative stress and inflammatory processes following MI ( 27 ). Large clinical studies have shown that SGLT2i decreases in the incidence of cardiovascular deaths and HF hospitalizations in patients with chronic HF ( 28 ).…”

Section: Discussionmentioning

confidence: 99%

Optimal treatment for post-MI heart failure in rats: dapagliflozin first, adding sacubitril-valsartan 2 weeks later

Tao

Yang

Zhang

et al. 2023

Front. Cardiovasc. Med.

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BackgroundBased on previous research, both dapagliflozin (DAPA) and sacubitril-valsartan (S/V) improve the prognosis of patients with heart failure (HF). Our study aims to investigate whether the early initiation of DAPA or the combination of DAPA with S/V in different orders would exert a greater protective effect on heart function than that of S/V alone in post-myocardial infarction HF (post-MI HF).MethodsRats were randomized into six groups: (A) Sham; (B) MI; (C) MI + S/V (1st d); (D) MI + DAPA (1st d); (E) MI + S/V (1st d) + DAPA (14th d); (F) MI + DAPA (1st d) + S/V (14th d). The MI model was established in rats via surgical ligation of the left anterior descending coronary artery. Histology, Western blotting, RNA-seq, and other approaches were used to explore the optimal treatment to preserve the heart function in post-MI HF. A daily dose of 1 mg/kg DAPA and 68 mg/kg S/V was administered.ResultsThe results of our study revealed that DAPA or S/V substantially improved the cardiac structure and function. DAPA and S/V monotherapy resulted in comparable reduction in infarct size, fibrosis, myocardium hypertrophy, and apoptosis. The administration of DAPA followed by S/V results in a superior improvement in heart function in rats with post-MI HF than those in other treatment groups. The administration of DAPA following S/V did not result in any additional improvement in heart function as compared to S/V monotherapy in rats with post-MI HF. Our findings further suggest that the combination of DAPA and S/V should not be administered within 3 days after acute myocardial infarction (AMI), as it resulted in a considerable increase in mortality. Our RNA-Seq data revealed that DAPA treatment after AMI altered the expression of genes related to myocardial mitochondrial biogenesis and oxidative phosphorylation.ConclusionsOur study revealed no notable difference in the cardioprotective effects of singular DAPA or S/V in rats with post-MI HF. Based on our preclinical investigation, the most effective treatment strategy for post-MI HF is the administration of DAPA during the 2 weeks, followed by the addition of S/V to DAPA later. Conversely, adopting a therapeutic scheme whereby S/V was administered first, followed by later addition of DAPA, failed to further improve the cardiac function compared to S/V monotherapy.

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Section: Discussionmentioning

confidence: 99%

Optimal treatment for post-MI heart failure in rats: dapagliflozin first, adding sacubitril-valsartan 2 weeks later

Tao

Yang

Zhang

et al. 2023

Front. Cardiovasc. Med.

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“…HDAC2 silencing affects the mRNA levels of calcium-activated potassium channels, resulting in delayed repolarization and prolonged action potentials [ 84 ]. Silencing of the HMT SUV39H1 can block the protective effect of sacubitril/valsartan on myocardial injury and heart failure after myocardial infarction [ 85 ]. SUV39H1 can bind to the promoter of the HDAC SIRT1 to inhibit its transcription of SIRT1, ultimately exacerbating the decline in cardiac function after ischemia–reperfusion injury.…”

Section: Role Of Chromatin Modifiers In Human Diseasesmentioning

confidence: 99%

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Nie,

Song,

Huang

et al. 2024

Mol Biomed

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The field of transcriptional regulation has revealed the vital role of chromatin modifiers in human diseases from the beginning of functional exploration to the process of participating in many types of disease regulatory mechanisms. Chromatin modifiers are a class of enzymes that can catalyze the chemical conversion of pyrimidine residues or amino acid residues, including histone modifiers, DNA methyltransferases, and chromatin remodeling complexes. Chromatin modifiers assist in the formation of transcriptional regulatory circuits between transcription factors, enhancers, and promoters by regulating chromatin accessibility and the ability of transcription factors to acquire DNA. This is achieved by recruiting associated proteins and RNA polymerases. They modify the physical contact between cis-regulatory factor elements, transcription factors, and chromatin DNA to influence transcriptional regulatory processes. Then, abnormal chromatin perturbations can impair the homeostasis of organs, tissues, and cells, leading to diseases. The review offers a comprehensive elucidation on the function and regulatory mechanism of chromatin modifiers, thereby highlighting their indispensability in the development of diseases. Furthermore, this underscores the potential of chromatin modifiers as biomarkers, which may enable early disease diagnosis. With the aid of this paper, a deeper understanding of the role of chromatin modifiers in the pathogenesis of diseases can be gained, which could help in devising effective diagnostic and therapeutic interventions.

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“…Notably, SPP1's association with cancer is profound, with its pivotal role in tumor invasion, metastasis, apoptosis, and angiogenesis documented extensively [4][5][6][7]. Shedding light on its significance in cardiovascular health, studies by Shen et al reveal that suppressing SPP1 leads to improvements in cardiac function, prevention of cardiac remodeling, reduction in oxidative stress and inflammation, and inhibition of cardiomyocyte apoptosis [8]. Recent investigations have also underscored the importance of SPP1, a cytokine, in the retina and optic nerve head.…”

Section: Introductionmentioning

confidence: 99%

Multi-Omics Reveals the Role of Osteopontin/Secreted Phosphoprotein 1 in Regulating Ovarian Aging

Hsu,

Li,

Lin

et al. 2024

JPM

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Secreted phosphoprotein 1 (SPP1), also known as osteopontin (OPN), is located on chromosome 4q22.1. This multifunctional secreted acidic glycoprotein is expressed intracellularly and extracellularly in various tissues, where it interacts with regulatory proteins and pro-inflammatory immune chemokines, contributing to the pathogenesis of multiple diseases. Nevertheless, the intricate genetic connections between SPP1 and ovarian aging remain largely unexplored. This study aims to bridge this knowledge gap by delving into ovarian aging and its associations with SPP1 using multi-omics data analysis. Our findings indicate that SPP1 is a potential gene related to ovarian aging. To comprehend the role of SPP1, we conducted spatial transcriptomic analyses on young and aged female mouse ovaries, revealing a significant decline in SPP1 expression in the aging group compared to the young group. Similarly, a significantly low level of SPP1 was found in the 73-year-old sample. Additionally, in-depth single-cell RNA-sequencing analysis identified associations between SPP1 and ITGAV, ITGB1, CD44, MMP3, and FN1. Notably, co-expression analysis highlighted a strong correlation between SPP1 and ITGB1. In summary, this study pioneers the identification of SPP1 as a gene implicated in ovarian aging. Further research into the role of SPP1 has the potential to advance precision medicine and improve treatment strategies for ovarian aging-related conditions.

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Sacubitril Valsartan Enhances Cardiac Function and Alleviates Myocardial Infarction in Rats through a SUV39H1/SPP1 Axis

Cited by 5 publications

References 38 publications

Optimal treatment for post-MI heart failure in rats: dapagliflozin first, adding sacubitril-valsartan 2 weeks later

Optimal treatment for post-MI heart failure in rats: dapagliflozin first, adding sacubitril-valsartan 2 weeks later

Chromatin modifiers in human disease: from functional roles to regulatory mechanisms

Multi-Omics Reveals the Role of Osteopontin/Secreted Phosphoprotein 1 in Regulating Ovarian Aging

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