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Swimming training in rats increases cardiac MicroRNA-126 expression and angiogenesis
Natan D DA Silva1, Tiago Fernandes, Ursula P R Soci
1Laboratory of Biochemistry and Molecular Biology of the Exercise, School of Physical Education and Sport, University of São Paulo, São Paulo, Brazil.
Purpose:
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.
Insights
Swimming training increases cardiac microRNA-126 (miRNA-126) expression, promoting angiogenesis. This enhances cardiac function by regulating vascular endothelial growth factor (VEGF) and its targets, supporting new blood vessel growth.
Area of Science:
- Cardiovascular Physiology
- Molecular Biology
- Exercise Science
Background:
- MicroRNA-126 (miRNA-126) is a key regulator of angiogenesis.
- It targets Sprouty-related protein 1 (Spred-1) and PI3K regulatory subunit 2 (PI3KR2), which inhibit angiogenesis via the VEGF pathway.
- The impact of exercise on cardiac miRNA-126 and its downstream effects on angiogenesis requires further investigation.
Purpose of the Study:
- To investigate the effect of swimming training on cardiac miRNA-126 expression.
- To determine the relationship between exercise-induced miRNA-126 levels and cardiac angiogenesis.
- To elucidate the molecular mechanisms by which swimming training influences angiogenic pathways in the heart.
Main Methods:
- Female Wistar rats were subjected to moderate (T1) and high (T2) volume swimming training for 10 weeks.
- Cardiac miRNA-126 and PI3KR2 gene expression were analyzed using real-time PCR.
- Protein levels of VEGF, Spred-1, Raf-1/ERK 1/2, and PI3K/Akt/eNOS were assessed, along with the capillary-fiber ratio.
Main Results:
- Swimming training significantly increased cardiac capillary-fiber ratio, VEGF protein expression, and miRNA-126 levels in both T1 and T2 groups.
- miRNA-126 expression correlated positively with angiogenesis markers.
- Training reduced Spred-1 and PI3KR2 levels, leading to activation of Raf-1/ERK 1/2 and PI3K/Akt/eNOS signaling pathways.
Conclusions:
- Aerobic exercise, specifically swimming, upregulates cardiac miRNA-126 expression.
- This increase in miRNA-126 contributes to exercise-induced cardiac angiogenesis.
- The mechanism involves indirect regulation of the VEGF pathway and direct modulation of its targets, enhancing MAPK and PI3K/Akt/eNOS angiogenic pathways.
