Physical inactivity increases oxidative stress, endothelial dysfunction, and atherosclerosis.

Area of Science:

• Cardiovascular Research
• Molecular Biology
• Exercise Physiology

Background:

• Sedentary lifestyles are linked to increased cardiovascular events, with mechanisms involving endothelial dysfunction and atherosclerosis.
• Reactive oxygen species (ROS), particularly from NADPH oxidase, play a key role in vascular pathologies.

Purpose of the Study:

• To investigate the molecular mechanisms linking physical inactivity to vascular dysfunction and atherosclerosis.
• To determine the role of NADPH oxidase and ROS in sedentary individuals compared to physically active ones.

Main Methods:

• C57BL6 mice were subjected to 6 weeks of physical inactivity or voluntary wheel running.
• Vascular ROS production, NADPH oxidase activity, and specific subunit expression were measured.
• Experiments were repeated in apolipoprotein E-deficient mice on a high-cholesterol diet to assess effects on atherosclerosis.

Main Results:

• Inactivity significantly increased vascular lipid peroxidation and superoxide release.
• NADPH oxidase activity, Rac1 activity, and expression of nox1, p47phox, and p67phox subunits were upregulated in sedentary mice.
• Physical inactivity accelerated atherosclerotic lesion formation and impaired endothelium-dependent vasorelaxation.

Conclusions:

• Inactivity enhances vascular NADPH oxidase expression and activity, leading to increased ROS production.
• Elevated ROS contributes to endothelial dysfunction and atherosclerosis in sedentary states.
• Regular physical activity counteracts these detrimental effects, promoting vascular health.