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      Effects on the Profile of Circulating miRNAs after Single Bouts of Resistance Training with and without Blood Flow Restriction—A Three-Arm, Randomized Crossover Trial

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          Abstract

          Background: The effects of blood flow restriction (training) may serve as a model of peripheral artery disease. In both conditions, circulating micro RNAs (miRNAs) are suggested to play a crucial role during exercise-induced arteriogenesis. We aimed to determine whether the profile of circulating miRNAs is altered after acute resistance training during blood flow restriction (BFR) as compared with unrestricted low- and high-volume training, and we hypothesized that miRNA that are relevant for arteriogenesis are affected after resistance training. Methods: Eighteen healthy volunteers (aged 25 ± 2 years) were enrolled in this three-arm, randomized-balanced crossover study. The arms were single bouts of leg flexion/extension resistance training at (1) 70% of the individual single-repetition maximum (1RM), (2) at 30% of the 1RM, and (3) at 30% of the 1RM with BFR (artificially applied by a cuff at 300 mm Hg). Before the first exercise intervention, the individual 1RM (N) and the blood flow velocity (m/s) used to validate the BFR application were determined. During each training intervention, load-associated outcomes (fatigue, heart rate, and exhaustion) were monitored. Acute effects (circulating miRNAs, lactate) were determined using pre-and post-intervention measurements. Results: All training interventions increased lactate concentration and heart rate ( p < 0.001). The high-intensity intervention (HI) resulted in a higher lactate concentration than both lower-intensity training protocols with BFR (LI-BFR) and without (LI) (LI, p = 0.003; 30% LI-BFR, p = 0.008). The level of miR-143-3p was down-regulated by LI-BFR, and miR-139-5p, miR-143-3p, miR-195-5p, miR-197-3p, miR-30a-5p, and miR-10b-5p were up-regulated after HI. The lactate concentration and miR-143-3p expression showed a significant positive linear correlation ( p = 0.009, r = 0.52). A partial correlation (intervention partialized) showed a systematic impact of the type of training (LI-BFR vs. HI) on the association ( r = 0.35 remaining after partialization of training type). Conclusions: The strong effects of LI-BFR and HI on lactate- and arteriogenesis-associated miRNA-143-3p in young and healthy athletes are consistent with an important role of this particular miRNA in metabolic processes during (here) artificial blood flow restriction. BFR may be able to mimic the occlusion of a larger artery which leads to increased collateral flow, and it may therefore serve as an external stimulus of arteriogenesis.

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          Dynamic regulation of circulating microRNA during acute exhaustive exercise and sustained aerobic exercise training.

          MicroRNAs (miRNAs) are intracellular mediators of essential biological functions. Recently, plasma-based 'circulating' miRNAs (c-miRNAs) have been shown to control cellular processes, but the c-miRNA response to human exercise remains unknown. We sought to determine whether c-miRNAs are dynamically regulated in response to acute exhaustive cycling exercise and sustained rowing exercise training using a longitudinal, repeated measures study design. Specifically, c-miRNAs involved in angiogenesis (miR-20a, miR-210, miR-221, miR-222, miR-328), inflammation (miR-21, miR-146a), skeletal and cardiac muscle contractility (miR-21, miR-133a), and hypoxia/ischaemia adaptation (miR-21, miR-146a, and miR-210) were measured at rest and immediately following acute exhaustive cycling exercise in competitive male rowers (n = 10, age = 19.1 ± 0.6 years) before and after a 90 day period of rowing training. Distinct patterns of c-miRNA response to exercise were observed and adhered to four major profiles: (1) c-miRNA up-regulated by acute exercise before and after sustained training (miR-146a and miR-222), (2) c-miRNA responsive to acute exercise before but not after sustained training (miR-21 and miR-221), (3) c-miRNA responsive only to sustained training (miR-20a), and (4) non-responsive c-miRNA (miR-133a, miR-210, miR-328). Linear correlations were observed between peak exercise levels of miR-146a and VO2max (r = 0.63, P = 0.003) and between changes in resting miR-20a and changes in VO2max (pre-training vs. post-training, r = 0.73; P = 0.02). Although future work is required, these results suggest the potential value of c-miRNAs as exercise biomarkers and their possible roles as physiological mediators of exercise-induced cardiovascular adaptation.
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            Hemodynamic and hormonal responses to a short-term low-intensity resistance exercise with the reduction of muscle blood flow.

            We investigated the hemodynamic and hormonal responses to a short-term low-intensity resistance exercise (STLIRE) with the reduction of muscle blood flow. Eleven untrained men performed bilateral leg extension exercise under the reduction of muscle blood flow of the proximal end of both legs pressure-applied by a specially designed belt (a banding pressure of 1.3 times higher than resting systolic blood pressure, 160-180 mmHg), named as Kaatsu. The intensity of STLIRE was 20% of one repetition maximum. The subjects performed 30 repetitions, and after a 20-seconds rest, they performed three sets again until exhaustion. The superficial femoral arterial blood flow and hemodynamic parameters were measured by using the ultrasound and impedance cardiography. Serum concentrations of growth hormone (GH), vascular endothelial growth factor (VEGF), noradrenaline (NE), insulin-like growth factor (IGF)-1, ghrelin, and lactate were also measured. Under the conditions with Kaatsu, the arterial flow was reduced to about 30% of the control. STLIRE with Kaatsu significantly increased GH (0.11+/-0.03 to 8.6+/-1.1 ng/ml, P < 0.01), IGF-1 (210+/-40 to 236+/-56 ng/ml, P < 0.01), and VEGF (41+/-13 to 103+/-38 pg/ml, P < 0.05). The increase in GH was related to neither NE nor lactate, but the increase in VEGF was related to that in lactate (r = 0.57, P < 0.05). Ghrelin did not change during the exercise. The maximal heart rate (HR) and blood pressure (BP) in STLIRE with Kaatsu were higher than that without Kaatsu. Stroke volume (SV) was lower due to the decrease of the venous return by Kaatsu, but, total peripheral resistance (TPR) did not change significantly. These results suggest that STLIRE with Kaatsu significantly stimulates the exercise-induced GH, IGF, and VEGF responses with the reduction of cardiac preload during exercise, which may become a unique method for rehabilitation in patients with cardiovascular diseases.
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              MicroRNA control of muscle development and disease.

              Cardiac and skeletal muscle development are controlled by evolutionarily conserved networks of transcription factors that coordinate the expression of genes involved in muscle growth, morphogenesis, differentiation, and contractility. In addition to regulating the expression of protein-coding genes, recent studies have revealed that myogenic transcription factors control the expression of a collection of microRNAs, which act through multiple mechanisms to modulate muscle development and function. In some cases, microRNAs fine-tune the expression of target mRNAs, whereas in other cases they function as 'on-off' switches. MicroRNA control of gene expression appears to be especially important during cardiovascular and skeletal muscle diseases, in which microRNAs participate in stress-dependent remodeling of striated muscle tissues. We review findings that point to the importance of microRNA-mediated control of gene expression during muscle development and disease, and consider the potential of microRNAs as therapeutic targets.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                02 July 2019
                July 2019
                : 20
                : 13
                : 3249
                Affiliations
                [1 ]Department of Sports Medicine, Institute of Sport Sciences, Goethe University, Ginnheimer Landstraße 39, 60487 Frankfurt, Germany
                [2 ]Department of Experimental Cardiology, Medical Faculty, Justus-Liebig-University, 35392 Giessen, Germany
                [3 ]Department of Cardiology, Kerckhoff Heart and Thorax Center, 61231 Bad Nauheim, Germany
                [4 ]German Center for Cardiovascular Research (DZHK), Partner Site RheinMain, Frankfurt am Main, Germany
                [5 ]Department of Vascular and Endovascular Surgery, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
                [6 ]Institute for Occupational Medicine, Social Medicine and Environmental Medicine, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany
                [7 ]Department of Pharmacology, Max-Planck-Institute for Heart and Lung Research, Ludwigstrasse 43, 61231 Bad Nauheim, Germany
                Author notes
                [* ]Correspondence: johvogel@ 123456em.uni-frankfurt.de (J.V.); kerstin.troidl@ 123456mpi-bn.mpg.de (K.T.); Tel.: +49-69-798-24426 (J.V.); +49-6032-7051205 (K.T.); Fax: +49-69-798-24592 (J.V.); +49-6032-7051204 (K.T.)
                Author information
                https://orcid.org/0000-0001-7477-0970
                https://orcid.org/0000-0002-6082-0006
                https://orcid.org/0000-0002-0883-9949
                Article
                ijms-20-03249
                10.3390/ijms20133249
                6651802
                31269677
                d437fdca-f1d6-4db7-9179-2e73ac3bb55a
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 31 May 2019
                : 28 June 2019
                Categories
                Article

                Molecular biology
                circulating mirna,mir-143-3p,blood flow restriction,peripheral artery disease,arteriogenesis,strength training

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