title: Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis.
abstract: OBJECTIVE
  MicroRNA (miRNA)-126 is angiogenic and has two validated targets: Sprouty-related protein 1 (Spred-1) and phosphoinositol-3 kinase regulatory subunit 2 (PI3KR2), negative regulators of angiogenesis by VEGF pathway inhibition. We investigated the role of swimming training on cardiac miRNA-126 expression related to angiogenesis.
  
  
  METHODS
  Female Wistar rats were assigned to three groups: sedentary (S), training 1 (T1, moderate volume), and training 2 (T2, high volume). T1 consisted of 60 min·d of swimming, five times per week for 10 wk with 5% body overload. T2 consisted of the same protocol of T1 until the eighth week; in the ninth week, rats trained for two times a day, and in the 10th week, rats trained for three times a day. MiRNA and PI3KR2 gene expression analysis was performed by real-time polymerase chain reaction in heart muscle. We assessed markers of training, the cardiac capillary-fiber ratio, cardiac protein expression of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS.
  
  
  RESULTS
  The cardiac capillary-fiber ratio increased in T1 (58%) and T2 (101%) compared with S. VEGF protein expression was increased 42% in T1 and 108% in T2. Cardiac miRNA-126 expression increased 26% (T1) and 42% (T2) compared with S, correlated with angiogenesis. The miRNA-126 target Spred-1 protein level decreased 41% (T1) and 39% (T2), which consequently favored an increase in angiogenic signaling pathway Raf-1/ERK 1/2. On the other hand, the gene expression of PI3KR2, the other miRNA-126 target, was reduced 39% (T1) and 78% (T2), and there was an increase in protein expression of components of the PI3K/Akt/eNOS signaling pathway in the trained groups.
  
  
  CONCLUSIONS
  This study showed that aerobic training promotes an increase in the expression of miRNA-126 and that this may be related to exercise-induced cardiac angiogenesis, by indirect regulation of the VEGF pathway and direct regulation of its targets that converged in an increase in angiogenic pathways, such as MAPK and PI3K/Akt/eNOS.
authors.affiliation: Laboratory of Biochemistry and Molecular Biology of the Exercise, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
authors.forename: Natan D
authors.initials: ND
authors.lastname: DA Silva
authors.forename: Tiago
authors.initials: T
authors.lastname: Fernandes
authors.forename: Ursula P R
authors.initials: UP
authors.lastname: Soci
authors.forename: Alex Willian A
authors.initials: AW
authors.lastname: Monteiro
authors.forename: M Ian
authors.initials: MI
authors.lastname: Phillips
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: DE Oliveira
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers; D005260:Female; D015870:Gene Expression; D035683:MicroRNAs / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D013550:Swimming; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D043925:Angiogenesis Inducing Agents; D015415:Biomarkers; D035683:MicroRNAs; D009419:Nerve Tissue Proteins; C404992:Spry2 protein, rat; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases