Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease

Author(s)

da Silva Jr, Natan D. D. ; Andrade-Lima, Aluisio ; Chehuen, Marcel R. R. ; Leicht, Anthony S. S. ; Brum, Patricia C. C. ; Oliveira, Edilamar M. M. ; Wolosker, Nelson ; Pelozin, Bruno R. A. ; Fernandes, Tiago ; Forjaz, Claudia L. M.

• Document type: Journal article
• Source: GENES; v. 14, n. 1, p. 9-pg., 2023-01-01.

Abstract

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 +/- 13 vs. 164 +/- 21 and CO = 100 +/- 8 vs. 106 +/- 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 +/- 13 vs. 130 +/- 5 and CO = 100 +/- 14 vs. 77 +/- 20%, p < 0.001; WT = 103 +/- 28 vs. 153 +/- 59 and CO = 100 +/- 36 vs. 84 +/- 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 +/- 23 vs. 75 +/- 21 and CO = 100 +/- 29 vs. 105 +/- 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway. (AU)

• FAPESP's process: 15/13800-0 - Walking training in intermittent claudication: responses at rest and after maximal exercise
• Grantee: Cláudia Lúcia de Moraes Forjaz
• Support Opportunities: Regular Research Grants
• FAPESP's process: 22/03138-2 - Functions and regulatory mechanisms of lincRNA-p21 in skeletal muscle: role on stem cell fate, myogenesis, trophism, contractility, exercise performance and injury repair
• Grantee: Tiago Fernandes
• Support Opportunities: Research Grants - Initial Project