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.

Highlights

  • Arteriogenesis is defined as the growth of functional collateral arteries from pre-existing arterioarteriolar anastomoses [1,2]

  • An initial trigger is the occlusion of a main artery, which occurs during peripheral artery disease (PAD)

  • Several mechano-sensors and transducers that convey the fluid shear stress (FSS) message during collateral remodeling have been proposed, including ion channels [5], the glycocalyx layer of endothelial cells (ECs) [6], nitric oxide (NO) [7], and microRNAs [8]. These small, non-coding ribonucleic acids have been shown to play a decisive role in processes such as heart development, vascular regeneration, and tissue repair [9,10,11,12]. micro RNAs (miRNAs) are involved in post-transcriptional gene regulation by binding to mRNAs, causing the repression of translation and mRNA degradation, fine-tuning protein expression

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Summary

Introduction

Arteriogenesis is defined as the growth of functional collateral arteries from pre-existing arterioarteriolar anastomoses [1,2]. Several mechano-sensors and transducers that convey the FSS message during collateral remodeling have been proposed, including ion channels [5], the glycocalyx layer of endothelial cells (ECs) [6], nitric oxide (NO) [7], and microRNAs (miRNAs) [8] These small, non-coding ribonucleic acids have been shown to play a decisive role in processes such as heart development, vascular regeneration, and tissue repair [9,10,11,12]. Despite the promising results derived from BFR as a method to mimic exercise effects under different occlusion conditions like PAD and the potential role of miRNAs as effectors after hemodynamic stress or FSS, nothing is known about the acute effects of strength training during BFR on miRNA levels. TThheebblolooddflfloowwvveelolocictiytyininththeeAA. .ppooppliltieteaawwaasssisgignnifiificacanntltylyreredduucecdedbbyywweaearirninggththeeBBFFRRcucuffff (c(coommppaarereddtotouunnrreesstrtricictetedd,,pp==0.00.0022; ;mmeaeanninintrtaraininddivivididuuaal lddififffeerreennccee: :−−7.76.6cmcm/s/,s−, 1−41%4%, F,iFgiugruere1)1. )

Basic Resistance Training Outcomes
Analysis of miRNAs in Different Training Intervention Groups
Associations between Training Outcomes and Circulating miRNAs
Discussion
Ethical Standard and Study Design
Sample
Experimental Design
Blood Flow Velocity Measurement
RM Determination
Intervention
Laboratory Analytic Outcomes
Self-Reported Outcomes
Findings
Data Analyses and Statistics
Full Text
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