‐Aerobic Swimming Training Changes Coronary Vascular Remodeling and MicroRNA Expression in Spontaneously Hypertensive Rats (SHR)‐
Authors: Roque Fernanda Roberta , Cho Henrique , Fernandes Tiago , das Neves Vander José , de Fátima Alves da Mota Glória , Rossoni Luciana Venturini , de Oliveira Edilamar Menezes 
Published: November 2023

‐We investigated the effect of aerobic swimming exercise training in vascular remodeling alterations of coronary artery from SHR and the microRNA expression patterns. All animal care and experimental procedure were in accordance with the National Institutes of Health Guidelines for the Care and Use of Laboratory Animals and approved by the local ethics committee of the University of São Paulo (N° 2013/01). The experimental groups (n=40) consisted of three‐month‐old male normotensive rats Wistar Kyoto (WKY), SHR and SHR trained (SHR‐t) on a swimming protocol for 10 weeks (60 min/ day ‐ 4% overload). Systolic blood pressure (SBP) and heart rate (HR) were evaluated using tail‐cuff pletysmography, and peak oxygen uptake (VO2) analyzing oxygen expired fraction (FeO2) during the progressive exercise test until exhaustion. The coronary structural properties were studied with a pressure myograph and microRNA array using FlashTagTM Biotin HSR RNA Labeling kit for analysis in Affymetrix 3.0 GeneChip miRNA Arrays. Swimming training reduces SBP (WKY 136± 2; SHR 201 ± 5; SHR‐t 183 ± 4 mmHg) and HR (WKY 455 ± 6; SHR 457 ± 9; SHR‐t 408 ± 8 bpm) and increases peak VO2 (WKY 72 ± 5; SHR 77 ± 5; SHR‐t 112 ± 10 ml.kg−1.min−1) in SHR. Vessel diameter and cross sectional area (CSA) of coronary arteries were similar in SHR and WKY, however, wall thickness and wall‐to‐lumen ratio were larger in SHR (p<0.001). Swimming training changes the altered structural parameters in SHR, increasing lumen (p<0.0001), vessel diameters (p<0.0001) and CSA (p<0.01). However, no changes in SHR‐t were observed in wall thickness and wall‐to‐lumen ratio compared to SHR. The parameters used for analysis of microRNA array detected 89 microRNAs differentially expressed in coronary arteries from SHR. Swimming training restores 16 microRNAs expression of which 9 were downregulated (microRNAs −485‐3p, −369‐5p, −135b‐3p, −489‐3p, −758‐5p, −208a‐3p, −148b‐5p, −101a‐5p, −328a‐5p) and 7 upregulated (microRNAs −361‐3p, −92a‐3p, −202‐3p, −351‐5p, −539‐5p, −370‐5p, −384‐3p) when compared to SHR control group. A bioinformatics study for functional analysis of the predicted targets genes for the 16 microRNA restored by swimming training demonstrated enrichment of different signaling pathways, including Mitogen‐Activated Protein Kinase (MAPK) (p value <0.001; Fold enrichment 1.96) and Wnt (p value < 0.01; Fold enrichment 2.02) dependent pathways. Both pathways play roles in phenotypic changes of vascular smooth muscle cells (VSMCs), regulating differentiation and proliferation, crucial for pathogenic vascular remodeling. Taken together the results suggest the role of aerobic swimming training regulating several microRNAs that may be related to signaling pathways involved in vascular remodeling control and inducing structural changes in coronary arteries in SHR.‐Support or Funding Information‐Financial support: FAPESP (2013/10472‐7 and 2010/50048‐1)‐