Dataset Information

Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice.

ABSTRACT: Background:Exercise benefits to cardiac rehabilitation (CR) following stable myocardial infarction (MI). The suitable exercise duration for aged patients with coronary heart disease (CHD) remains controversial, and the underlying molecular mechanism is still unclear. Methods and Results:18-Month-old mice after stable MI were randomly submitted to different durations of exercise, including 15 and 60?min swimming training (ST) once per day, five times a week for 8 weeks. Compared to sedentary mice, 15?min ST, rather than 60?min ST, significantly augmented left ventricular function, increased survival rate, and suppressed myocardial fibrosis and apoptosis. 15?min ST improved mitochondrial morphology via regulating mitochondrial fission-fusion signaling. 15?min ST regulated mitophagy signaling via inhibiting LC3-II and P62 levels and increasing PINK/Parkin expression. 15?min ST also inhibited ROS production and enhanced antioxidant SOD2 activity. Notably, 15?min ST significantly increased sirtuin (SIRT) 3 level (2.7-fold) in vivo while the inhibition of SIRT3 exacerbated senescent H9c2 cellular LDH release and ROS production under hypoxia. In addition, SIRT3 silencing impairs mitochondrial dynamics and mitophagy in senescent cardiomyocytes against simulated ischemia (SI) injury. Conclusion:Collectively, our study demonstrated for the first time that sustained short-duration exercise, rather than long-duration exercise, attenuates cardiac dysfunction after MI in aged mice. It is likely that the positive regulation induced by a short-duration ST regimen on the elevated SIRT3 protein level improved mitochondrial quality control and decreased apoptosis and fibrosis contributed to the observed more resistant phenotype.

SUBMITTER: Zhao D

PROVIDER: S-EPMC5925211 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice.

Zhao Dajun D Sun Yang Y Tan Yanzhen Y Zhang Zhengbin Z Hou Zuoxu Z Gao Chao C Feng Pan P Zhang Xing X Yi Wei W Gao Feng F

Oxidative medicine and cellular longevity 20180411

<h4>Background</h4>Exercise benefits to cardiac rehabilitation (CR) following stable myocardial infarction (MI). The suitable exercise duration for aged patients with coronary heart disease (CHD) remains controversial, and the underlying molecular mechanism is still unclear.<h4>Methods and results</h4>18-Month-old mice after stable MI were randomly submitted to different durations of exercise, including 15 and 60 min swimming training (ST) once per day, five times a week for 8 weeks. Compared to ...[more]

PMID: 29849892

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Project description:In spite of early interventions to treat acute myocardial infarction (MI), the occurrence of adverse cardiac remodeling following heart failure due to acute MI remains a clinical challenge. Thus, there is an increasing demand for the development of novel therapeutic agents capable of inhibiting the development of pathological ventricular remodeling. RNA-seq data analysis of acute MI rat models from GEO revealed that Runx1 was the most differentially expressed MI-related gene. In this study, we demonstrated that increased Runx1 expression under pathological conditions results in decreased cardiac contractile function. We identified dihydrolycorine, an alkaloid lycorine, as a promising inhibitor of Runx1. Our results showed that treatment with this drug could prevent adverse cardiac remodeling, as indicated by the downregulation of fibrotic genes using western blotting (collagen I, TGFβ, and p-smad3), downregulation of the apoptosis gene Bax, upregulation of the apoptosis gene Bcl-2, and improved cardiac functions, such as LVEF, LVSF, LVESD, and LVEDD. Additionally, dihydrolycorine treatment could rescue cardiomyocyte hypertrophy as demonstrated by wheat germ agglutinin staining, increased expression levels of the punctuate gap junction protein connexin 43, and decreased α-SMA expression, resulting in cardiomyocyte fibrosis in immunofluorescence staining. Molecular docking, binding modeling, and pull-down assays were used to identify potential dihydrolycorine-binding sites in Runx1. When Ad-sh-Runx1 was transfected into hypoxia-cardiomyocytes or injected into the hearts of MI rats, the cardioprotective effects of dihydrolycorine were abolished, and the normal electrophysiological activity of cardiomyocytes was disrupted. Taken together, the results of the present study indicate that dihydrolycorine may inhibit adverse cardiac remodeling after MI through the reduction of Runx1, suggesting that dihydrolycorine-mediated-Runx1 regulation might represent a novel therapeutic approach for adverse cardiac remodeling after MI.

Project description:BACKGROUND: Cell therapy approaches for biologic cardiac repair hold great promises, although basic fundamental issues remain poorly understood. In the present study we examined the effects of timing and routes of administration of bone marrow cells (BMC) post-myocardial infarction (MI) and the efficacy of an injectable biopolymer scaffold to improve cardiac cell retention and function. METHODOLOGY/PRINCIPAL FINDINGS: (99m)Tc-labeled BMC (6 x 10(6) cells) were injected by 4 different routes in adult rats: intravenous (IV), left ventricular cavity (LV), left ventricular cavity with temporal aorta occlusion (LV(+)) to mimic coronary injection, and intramyocardial (IM). The injections were performed 1, 2, 3, or 7 days post-MI and cell retention was estimated by gamma-emission counting of the organs excised 24 hs after cell injection. IM injection improved cell retention and attenuated cardiac dysfunction, whereas IV, LV or LV* routes were somewhat inefficient (<1%). Cardiac BMC retention was not influenced by timing except for the IM injection that showed greater cell retention at 7 (16%) vs. 1, 2 or 3 (average of 7%) days post-MI. Cardiac cell retention was further improved by an injectable fibrin scaffold at day 3 post-MI (17 vs. 7%), even though morphometric and function parameters evaluated 4 weeks later displayed similar improvements. CONCLUSIONS/SIGNIFICANCE: These results show that cells injected post-MI display comparable tissue distribution profile regardless of the route of injection and that there is no time effect for cardiac cell accumulation for injections performed 1 to 3 days post-MI. As expected the IM injection is the most efficient for cardiac cell retention, it can be further improved by co-injection with a fibrin scaffold and it significantly attenuates cardiac dysfunction evaluated 4 weeks post myocardial infarction. These pharmacokinetic data obtained under similar experimental conditions are essential for further development of these novel approaches.

Dataset Information

Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice.

Publications

Short-Duration Swimming Exercise after Myocardial Infarction Attenuates Cardiac Dysfunction and Regulates Mitochondrial Quality Control in Aged Mice.

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