A New Secretory Peptide of Natriuretic Peptide Family, Osteocrin, Suppresses the Progression of Congestive Heart Failure After Myocardial Infarction

Miyazaki, Takahiro; Otani, Kentaro; Chiba, Ayano; Nishimura, Hirokazu; Tokudome, Takeshi; Takano-Watanabe, Haruko; Matsuo, Akihiko; Ishikawa, Hiroyuki; Shimamoto, Keiko; Fukui, Hajime; Kanai, Yugo; Yasoda, Akihiro; Ogata, Soshiro; Nishimura, Kunihiro; Minamino, Naoto; Mochizuki, Naoki

doi:10.1161/circresaha.117.312624

Cited by 47 publications

(77 citation statements)

References 50 publications

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“…Our findings indicate increased expression of musclin in cardiac muscle of the HIIT group as compared with both other groups (Figure 3a-c). The underlying mechanism of this molecule is still unclear, however, it is interesting that we observe an increase in expression in exercise groups and a previous study showing the benefits of osteocrin in CHF models (Miyazaki et al, 2018). A possible explanation for a link between exercise, musclin and PGC-1a was previously suggested.…”

Section: Discussionsupporting

confidence: 62%

“…This protein is mainly expressed in skeletal muscle and is released as a myokine; however, a recent study showed the expression of musclin in the zebrafish heart (Chiba et al, ). In addition, intravenous infusion of osteocrin in mouse models of congestive heart failure (CHF) showed a by reducing fibrosis and inflammation (Miyazaki et al, ). Our findings indicate increased expression of musclin in cardiac muscle of the HIIT group as compared with both other groups (Figure a–c).…”

Section: Discussionmentioning

confidence: 99%

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Cardioprotective effects of high‐intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways

Jeremić

Weber

Theilen

et al. 2019

Journal Cellular Physiology

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Human studies have shown high‐intensity interval training (HIIT) has beneficial cardiovascular effects and is typically more time‐efficient compared with traditional endurance exercise. The main goal of this study is to show the potential molecular and functional cardiovascular benefits of HIIT compared with endurance training (ET). Three groups of mice were used including sedentary‐control, ET mice, and HIIT mice groups. Results indicated ejection fraction was increased in HIIT compared with ET while fractional shortening was increased in the HIIT group compared with both groups. Blood flow of the abdominal aorta was increased in both exercise groups compared with control. Increases in cross‐sectional area and mitochondrial and antioxidative markers in HIIT compared with control were observed, along with several microRNAs. These findings indicate HIIT has specific cardiac‐protective effects and may be a viable alternative to traditional ET as a cardiovascular preventative medicine intervention.

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Section: Discussionsupporting

confidence: 62%

Section: Discussionmentioning

confidence: 99%

Cardioprotective effects of high‐intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways

Jeremić

Weber

Theilen

et al. 2019

Journal Cellular Physiology

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“…In mice, the cardiovascular phenotype of NPR-C LoF has not been investigated, although chronic and sustained blockade of NPR-C inhibits cardiac fibrosis and remodeling. 55 In two Npr3 mutant mouse models, sudden death has been reported. 31,32 In our study, progressive aortic dilatation was observed in the older two subjects (Supplemental Note).…”

mentioning

confidence: 99%

Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities

Boudin

Jong

Prickett

et al. 2018

The American Journal of Human Genetics

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The natriuretic peptide signaling pathway has been implicated in many cellular processes, including endochondral ossification and bone growth. More precisely, different mutations in the NPR-B receptor and the CNP ligand have been identified in individuals with either short or tall stature. In this study we show that the NPR-C receptor (encoded by NPR3) is also important for the regulation of linear bone growth. We report four individuals, originating from three different families, with a phenotype characterized by tall stature, long digits, and extra epiphyses in the hands and feet. In addition, aortic dilatation was observed in two of these families. In each affected individual, we identified a bi-allelic loss-of-function mutation in NPR3. The missense mutations (c.442T>C [p.Ser148Pro] and c.1088A>T [p.Asp363Val]) resulted in intracellular retention of the NPR-C receptor and absent localization on the plasma membrane, whereas the nonsense mutation (c.1524delC [p.Tyr508]) resulted in nonsense-mediated mRNA decay. Biochemical analysis of plasma from two affected and unrelated individuals revealed a reduced NTproNP/NP ratio for all ligands and also high cGMP levels. These data strongly suggest a reduced clearance of natriuretic peptides by the defective NPR-C receptor and consequently increased activity of the NPR-A/B receptors. In conclusion, this study demonstrates that loss-of-function mutations in NPR3 result in increased NPR-A/B signaling activity and cause a phenotype marked by enhanced bone growth and cardiovascular abnormalities.

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“…The biological effect of musclin is mediated through increased circulating levels of NP A, which binds to NPR1 and activates GPCR and PGC-1α pathways ( Moffatt et al, 2007 ; Subbotina et al, 2015 ; Chiba et al, 2016 ). Recent study showed that musclin exhibits cardioprotective role and reduces acute inflammation after myocardial infarction in mice ( Miyazaki et al, 2018 ). Musclin might affect local concentrations of NPs and augment cardiac function by decreasing the preload and exerting anti-inflammatory effects in failing heart ( Kiemer and Vollmar, 2001 ).…”

Section: Discussionmentioning

confidence: 99%

“…Musclin could be insensitive to plasma membrane-bound neutral endopeptidase (NEP) that breaks the Cys–Cys bond for the ring structure of NPs. Because both musclin and NPs bind to NPR3, the former can inhibit the clearance of NPs and enhance NP-dependent signaling in NPR3-expressing tissues ( Miyazaki et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

The Effects of PPAR Stimulation on Cardiac Metabolic Pathways in Barth Syndrome Mice

et al. 2018

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Aim: Tafazzin knockdown (TazKD) in mice is widely used to create an experimental model of Barth syndrome (BTHS) that exhibits dilated cardiomyopathy and impaired exercise capacity. Peroxisome proliferator-activated receptors (PPARs) are a group of nuclear receptor proteins that play essential roles as transcription factors in the regulation of carbohydrate, lipid, and protein metabolism. We hypothesized that the activation of PPAR signaling with PPAR agonist bezafibrate (BF) may ameliorate impaired cardiac and skeletal muscle function in TazKD mice. This study examined the effects of BF on cardiac function, exercise capacity, and metabolic status in the heart of TazKD mice. Additionally, we elucidated the impact of PPAR activation on molecular pathways in TazKD hearts.Methods: BF (0.05% w/w) was given to TazKD mice with rodent chow. Cardiac function in wild type-, TazKD-, and BF-treated TazKD mice was evaluated by echocardiography. Exercise capacity was evaluated by exercising mice on the treadmill until exhaustion. The impact of BF on metabolic pathways was evaluated by analyzing the total transcriptome of the heart by RNA sequencing.Results: The uptake of BF during a 4-month period at a clinically relevant dose effectively protected the cardiac left ventricular systolic function in TazKD mice. BF alone did not improve the exercise capacity however, in combination with everyday voluntary running on the running wheel BF significantly ameliorated the impaired exercise capacity in TazKD mice. Analysis of cardiac transcriptome revealed that BF upregulated PPAR downstream target genes involved in a wide spectrum of metabolic (energy and protein) pathways as well as chromatin modification and RNA processing. In addition, the Ostn gene, which encodes the metabolic hormone musclin, is highly induced in TazKD myocardium and human failing hearts, likely as a compensatory response to diminished bioenergetic homeostasis in cardiomyocytes.Conclusion: The PPAR agonist BF at a clinically relevant dose has the therapeutic potential to attenuate cardiac dysfunction, and possibly exercise intolerance in BTHS. The role of musclin in the failing heart should be further investigated.

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A New Secretory Peptide of Natriuretic Peptide Family, Osteocrin, Suppresses the Progression of Congestive Heart Failure After Myocardial Infarction

Abstract: OSTN might suppress the worsening of CHF after MI by inhibiting clearance of NP family peptides.

Cited by 47 publications

References 50 publications

Cardioprotective effects of high‐intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways

Cardioprotective effects of high‐intensity interval training are mediated through microRNA regulation of mitochondrial and oxidative stress pathways

Bi-allelic Loss-of-Function Mutations in the NPR-C Receptor Result in Enhanced Growth and Connective Tissue Abnormalities

The Effects of PPAR Stimulation on Cardiac Metabolic Pathways in Barth Syndrome Mice

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