Effects of Exercise-Induced Irisin on Cardiac Fibrosis Resulted from the Combination of Obesity and Intermittent Hypoxia in Rats

2017 ◽  
Vol 19 (3) ◽  
pp. 272-287
Author(s):  
Tsung-I Chen
Keyword(s):  
Intermittent Hypoxia ◽  
Cardiac Fibrosis ◽  
Exercise Induced

scholarly journals Combination of Broccoli Sprout Extract and Zinc Provides Better Protection against Intermittent Hypoxia-Induced Cardiomyopathy Than Monotherapy in Mice

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Jiqun Wang ◽  
Jian Zhang ◽  
Liping Chen ◽  
Jun Cai ◽  
Zhijie Li ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cardiac Fibrosis ◽  
Combined Treatment ◽  
Chronic Intermittent Hypoxia ◽  
Related Factor ◽  
Protective Effects ◽  
Antioxidative Stress ◽  
Dual Activation ◽  
First Time ◽  
Broccoli Sprout

Nuclear factor-E2-related factor 2 (Nrf2) and metallothionein have each been reported to protect against chronic intermittent hypoxia- (IH-) induced cardiomyopathy. Sulforaphane-rich broccoli sprout extract (BSE) and zinc can effectively induce Nrf2 and metallothionein, respectively, to protect against IH-induced cardiomyopathy via antioxidative stress. However, whether the cardiac protective effects of the combination of BSE and zinc can be synergistic or the same has not been evaluated. In this study, we treated 8-week-old C57BL/6J mice with BSE and/or zinc during exposure to IH for 8 weeks. Cardiac dysfunction, as determined by echocardiography, and pathological remodeling and abnormalities, including cardiac fibrosis, inflammation, and oxidative damage, examined by histopathology and western blotting, were clearly observed in IH mice but were not significant in IH mice treated with either BSE, zinc, or zinc/BSE. Furthermore, the effects of the combined treatment with BSE and zinc were always greater than those of single treatments. Nrf2 function and metallothionein expression in the heart increased to a greater extent using the combination of BSE and zinc than using BSE or zinc alone. These findings for the first time indicate that the dual activation of Nrf2 and metallothionein by combined treatment with BSE and zinc may be more effective than monotherapy at preventing the development of IH-induced cardiomyopathy.

Abstract 220: miR-486 Mediates the Benefits of Exercise in Attenuating Cardiac Fibrosis

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Dongchao Lv ◽  
Yihua Bei ◽  
Qiulian Zhou ◽  
Qi Sun ◽  
Tianzhao Xu ◽  
...  
Keyword(s):  
Cardiac Fibrosis ◽  
Cardiac Fibroblasts ◽  
Mrna Level ◽  
Neonatal Rat ◽  
Cardiac Growth ◽  
Non Coding Rnas ◽  
Exercise Induced ◽  
Proliferation Assays

MicroRNAs (miRNAs, miRs), a novel group of small non-coding RNAs, play important roles in cardiac fibrosis. Exercise-induced physiological cardiac growth is associated with hypertrophy and proliferation of cardiomyocytes. In addition, exercise has been shown to inhibit cardiac fibrosis. However, relative little is known about whether exercise could attenuating cardiac fibrosis via targeting miRNA. miR-486 is a muscle enriched miRNAs, however, its role in heart is relative unclear. The current study aimed to investigate the role of miR-486 in exercise-induced cardiac growth in a 3-week swimming training murine model as well as in the function of cardiac fibroblasts and production of extracellular matrix (ECM) using neonatal rat cardiac fibroblasts in primary culture. Our data showed that exercised mice displayed increased about three-fold expression of miR-486 in hearts as measured by microarray analysis and qRT-PCRs. EdU proliferation assays demonstrated that miR-486 mimics decreased (5.90%±0.57% vs 4.02%±0.27% in nc-mimics vs miR-486-mimics, respectively), while miR-486 inhibitor increased the proliferation of cardiac fibroblasts in vitro (5.87%±0.16% vs 9.60%±0.58% in nc-inhibitor vs miR-486-inhibitor, respectively). Although downregulation of miR-486 had no regulatory effect on α-sma and collagen-1 gene expression in cardiac fibroblasts, overexpression of miR-486 significantly reduced the mRNA level of α-sma (1.01±0.08 vs 0.28±0.04 in nc-mimics vs miR-486-mimics, respectively) and collagen-1(1.02±0.12 vs 0.58±0.09 in nc-mimics vs miR-486-mimics, respectively), indicative of attenuated activation of fibroblasts and reduced production of ECM. These data reveal that miR-486 is essentially involved in the proliferation and activation of cardiac fibroblasts, and might be a key regulator mediating the benefit of exercise in preventing cardiac fibrosis.

Effects of intermittent hypoxia on SaO2, cerebral and muscle oxygenation during maximal exercise in athletes with exercise-induced hypoxemia

2007 ◽  
Vol 104 (2) ◽  
pp. 383-393 ◽  
Author(s):  
Helen C. Marshall ◽  
Michael J. Hamlin ◽  
John Hellemans ◽  
Carissa Murrell ◽  
Nik Beattie ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Maximal Exercise ◽  
Muscle Oxygenation ◽  
Exercise Induced

Intermittent Hypoxia Increases Mitochondrial Dynamics and Biogenesis After Eccentric Exercise-Induced Muscle Damage in Trained Rats

2016 ◽  
Vol 48 ◽  
pp. 899-900
Author(s):  
David Rizo-Roca ◽  
Estela Santos-Alves ◽  
Juan Gabriel Ríos-Kristjánsson ◽  
Cristian Núñez-Espinosa ◽  
Antonio Ascensão ◽  
...  
Keyword(s):  
Muscle Damage ◽  
Eccentric Exercise ◽  
Intermittent Hypoxia ◽  
Mitochondrial Dynamics ◽  
Exercise Induced

scholarly journals Intermittent hypoxia mediated by TSP1 dependent on STAT3 induces cardiac fibroblast activation and cardiac fibrosis

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Qiankun Bao ◽  
Bangying Zhang ◽  
Ya Suo ◽  
Chen Liu ◽  
Qian Yang ◽  
...  
Keyword(s):  
Intermittent Hypoxia ◽  
Cardiac Fibrosis ◽  
Synergistic Effects ◽  
Cardiac Fibroblasts ◽  
Cardiac Fibroblast ◽  
Ang Ii ◽  
Fibroblast Activation ◽  
Obstructive Sleep

Intermittent hypoxia (IH) is the predominant pathophysiological disturbance in obstructive sleep apnea (OSA), known to be independently associated with cardiovascular diseases. However, the effect of IH on cardiac fibrosis and molecular events involved in this process are unclear. Here, we tested IH in angiotensin II (Ang II)-induced cardiac fibrosis and signaling linked to fibroblast activation. IH triggered cardiac fibrosis and aggravated Ang II-induced cardiac dysfunction in mice. Plasma thrombospondin-1 (TSP1) content was upregulated in both IH-exposed mice and OSA patients. Moreover, both in vivo and in vitro results showed IH-induced cardiac fibroblast activation and increased TSP1 expression in cardiac fibroblasts. Mechanistically, phosphorylation of STAT3 at Tyr705 mediated the IH-induced TSP1 expression and fibroblast activation. Finally, STAT3 inhibitor S3I-201 or AAV9 carrying a periostin promoter driving the expression of shRNA targeting Stat3 significantly attenuated the synergistic effects of IH and Ang II on cardiac fibrosis in mice. This work suggests a potential therapeutic strategy for OSA-related fibrotic heart disease.

Abstract 238: miR-222 is Necessary for Exercise-induced Cardiac Growth and Protects Against Pathological Cardiac Remodeling

2014 ◽  
Vol 115 (suppl_1) ◽  
Author(s):  
Xiaojun Liu ◽  
Junjie Xiao ◽  
Han Zhu ◽  
Xin Wei ◽  
Colin Platt ◽  
...  
Keyword(s):  
Cardiac Remodeling ◽  
Cardiac Fibrosis ◽  
Ischemia Reperfusion ◽  
Site Directed Mutagenesis ◽  
Neonatal Rat ◽  
Proliferation Markers ◽  
Cardiac Growth ◽  
Adverse Remodeling ◽  
Heart Size ◽  
Exercise Induced

Exercise induces cardiac growth, protects against adverse remodeling, and may also induce a regenerative response. Since microRNAs (miRNA) play important roles in cardiovascular disease, we investigated their role in the cardiac exercise response. We used the TaqMan rodent miRNA array to profile cardiac miRNA expressed at three weeks in two exercise models (swimming, running) compared to sedentary controls. Sixteen concordantly regulated miRNAs were identified and validated in both models, and examined for functional effects in neonatal rat ventricular cardiomyocytes (CMs). miR-222 was upregulated ~two-fold in both models and increased CM size (22%, p<0.01) and proliferation markers (EdU and Ki67, p<0.01). Bioinformatic and expression analyses identified four potential miR-222 targets (p27, Hipk1, Hipk2, and Hmbox-1) in CMs. These were confirmed as direct targets by luciferase assays, site-directed mutagenesis, and immunoblotting. siRNA knockdown (KD) of p27 or Hipk1 induced neonatal CM proliferation, while siRNA KD of Hmbox-1 increased CM size. To examine miR-222’s role in vivo, LNA-antimiR-222 was injected via tail vein or subcutaneously and shown to reduce cardiac miR-222 levels to 1.5% (p<0.01). Untreated animals subjected to three weeks of swimming had the expected increase in heart size (15% in HW/TL, p<0.05), CM size (26%, p<0.05), and markers of CM proliferation (Ki67 and pHH3, p<0.05). Increases in heart and CM size were unaffected by control LNA-antimiR but completely blocked by LNA-antimiR-222, while CM proliferation markers decreased (60%, p<0.05). To see if miR-222 is sufficient to mediate the benefits of exercise, we made transgenic mice with cardiac-specific, regulated expression of miR-222 (Tg-miR-222). Tg-miR-222 have normal heart size and function at baseline. After ischemia-reperfusion injury (IRI), Tg-miR-222 had similar initial dysfunction but were protected against adverse remodeling over the next six weeks with better function (p<0.01), less cardiac fibrosis (68%, p<0.05), and increased CM proliferation markers (63%, p<0.05). Conclusion: Cardiac miR-222 is upregulated by exercise, necessary for exercise-induced cardiac growth, and protects against pathological cardiac remodeling after IRI.

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