Hypercholesterolemia impairs exercise capacity in mice.

Area of Science:

• Cardiovascular Physiology
• Metabolic Disorders
• Exercise Science

Background:

• Hypercholesterolemia is linked to cardiovascular dysfunction.
• Previous studies indicated impaired exercise hyperemia and aerobic capacity in hypercholesterolemic mice.

Purpose of the Study:

• To investigate the temporal and quantitative relationship between hypercholesterolemia and aerobic/anaerobic capacity.
• To explore the mechanisms underlying exercise dysfunction in hypercholesterolemia.

Main Methods:

• Utilized wild type and apoE knockout mice fed regular or high-fat diets to induce varying cholesterol levels.
• Assessed exercise capacity using treadmill ergospirometry at different ages.
• Measured aortic vasodilator function, nitric oxide (NOx) activity and excretion, muscle microvascular density, citrate synthase activity, and myocardial characteristics.

Main Results:

• Aerobic exercise capacity progressively declined in hypercholesterolemic mice from 12 to 20 weeks of age.
• Anaerobic capacity was unaffected by hypercholesterolemia.
• Aerobic dysfunction correlated with serum cholesterol levels and was associated with reduced nitric oxide-mediated vascular function.

Conclusions:

• Aerobic exercise dysfunction is evident in murine models of genetic and diet-induced hypercholesterolemia.
• Reduced vascular nitric oxide production is a key mechanism associated with this aerobic exercise impairment.