Chronic Exercise Training Improved Aortic Endothelial and Mitochondrial Function via an AMPKα2-Dependent Manner.

Area of Science:

• Cardiovascular Physiology
• Molecular Biology
• Exercise Science

Background:

• Chronic exercise training confers vascular protection, but the specific molecular mechanisms are not fully understood.
• Adenosine monophosphate-activated protein kinase α2 (AMPKα2) is a key cellular energy sensor implicated in various physiological processes.

Purpose of the Study:

• To investigate the role of AMPKα2 in exercise-induced improvements in aortic endothelial and mitochondrial function.
• To elucidate the molecular pathways through which AMPKα2 mediates vascular protection during chronic exercise.

Main Methods:

• Utilized AMPKα2 knockout (AMPKα2^-/-) and wild-type (WT) mice subjected to a 6-week treadmill running protocol.
• Assessed thoracic aorta function, including vasodilation, endothelial nitric oxide synthase (eNOS) activity, mitochondrial content (Complex I, mtDNA), autophagy markers (BNIP3L, LC3B), and antioxidant enzyme expression (MnSOD, catalase).

Main Results:

• Exercise training significantly improved vasodilation and increased eNOS phosphorylation in WT mice, effects absent in AMPKα2^-/- mice.
• Exercise enhanced thoracic aortic mitochondrial content and antioxidant capacity (MnSOD, catalase) in WT mice, linked to reduced autophagy markers (BNIP3L, LC3B), but these benefits were abolished in AMPKα2^-/- mice.
• AMPKα2 expression and phosphorylation were increased by exercise in WT mice, correlating with improved vascular function.

Conclusions:

• AMPKα2 is essential for exercise-induced vascular protection, mediating improvements in endothelial and mitochondrial function.
• AMPKα2 activation by exercise enhances aortic antioxidant capacity and mitochondrial biogenesis while potentially suppressing mitochondrial autophagy.
• These findings highlight AMPKα2 as a critical molecular target for understanding and promoting exercise-related cardiovascular benefits.