Aaron Wallace; Brad Hauck; Michelle White; Michele Hansen, University of Utah
Our laboratory is determining the contribution from endothelial cell (EC) autophagy to aging-associated endothelial dysfunction. Autophagy is a process whereby damaged cellular cargo is delivered to the lysosome for degradation and eventual recycling or removal. Data from our laboratory indicate that: (i) autophagy occurs in ECs and arteries; (ii) autophagy-related (Atg) mRNA in ECs and protein expression in arteries is lower in old (22 months) vs. adult (7 months) mice; (iii) endothelial dysfunction displayed by arteries from old vs. adult mice is rescued by pharmacological activation of autophagy; and (iv) exercise-training upregulates vascular autophagy in adult mice. Thus, robust rationale is provided to test the hypothesis that exercise-training lessens endothelial dysfunction displayed by old mice by increasing vascular autophagy. 21-month old male C57Bl6 mice were familiarized with treadmill running for 2 days. On days 3 and 4, all mice completed a body composition assessment (nuclear magnetic resonance;NMR) and a maximal exercise test wherein total work performed was calculated. Next, animals ran on a motorized treadmill 6 x per week x 15-60-min per session @ 10-20% grade x 11.5 weeks (ETR, n=12) or remained sedentary (SED, n=6). SED mice maintained familiarity with treadmill-running by completing 1 x 15-min bout per week. After 11.5 weeks NMR and maximal exercise tests were repeated on all mice. Additionally, myocardial function was evaluated using echocardiography, indices of autophagy-related EC mRNA (RT-PCR) and arterial protein (immunoblotting) were estimated, and arterial function was quantified using isobaric and isometric procedures. Total work (kgm) performed during the maximal exercise test at 11.5 weeks was greater (p