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

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Exercise Science

Background:

• Peripheral artery disease (PAD) is characterized by reduced muscle capillary density, impairing walking ability.
• Current recommendations for PAD patients include walking training (WT) to improve functional capacity.
• The molecular mechanisms underlying WT-induced adaptations in PAD muscles are not fully understood.

Purpose of the Study:

• To determine if walking training (WT) promotes angiogenesis in PAD-affected muscles.
• To investigate the role of microRNA-126 (miRNA-126) and vascular endothelial growth factor (VEGF) in WT-induced angiogenesis in PAD.
• To explore the involvement of the PI3K/Akt signaling pathway, specifically PI3KR2, in these adaptations.

Main Methods:

• Thirty-two men with PAD were randomized into a walking training (WT) group (n=16) or a control (CO) group (n=16).
• Intervention lasted 12 weeks with 2 WT sessions per week.
• Maximal treadmill tests and gastrocnemius muscle biopsies were analyzed for histological and molecular markers, including capillary-fiber ratio, miRNA-126, VEGF, and PI3KR2 expression.

Main Results:

• WT significantly increased maximal walking capacity by 65% and the gastrocnemius capillary-fiber ratio (p < 0.001).
• Muscular expression of miRNA-126 and VEGF increased significantly in the WT group (p < 0.001).
• Expression of PI3KR2, a negative regulator of angiogenesis, decreased in the WT group (p = 0.021).

Conclusions:

• Walking training effectively promotes angiogenesis in the skeletal muscle of PAD patients.
• miRNA-126 plays a crucial role in WT-induced angiogenesis, potentially by inhibiting PI3KR2 and facilitating VEGF signaling.
• These findings highlight molecular targets for enhancing exercise therapy in PAD management.