Exercise‐training attenuates endothelial dysfunction and repressed vascular autophagy associated with aging in mice
Authors: Cho Jae Min , Park Seul‐Ki , Wallace Aaron , Hauck Brad , White Michelle , Hansen Michele , Symons J David 
Published: June 2021

Autophagy is a process whereby damaged cellular cargo is delivered to the lysosome for degradation and eventual recycling or removal. A reduction of autophagy‐related mRNA and protein expression in endothelial cells (ECs) from old rodents and humans is associated with arterial dysfunction. Exercise‐training could provide a physiological stimulus to improve vascular health by upregulating EC autophagy. For example, earlier we reported that basal mRNA and protein expression of autophagy‐related genes is elevated (p<0.05) in the vasculature of trained vs. sedentary adult (i.e., 5–6 months old) male mice (FASEB J, 31:1, 840–25, 2017). Here we tested the hypothesis that exercise‐training attenuates endothelial dysfunction and repressed vascular autophagy associated with aging. 21‐month old C57Bl6 male mice did (ETR, n=12) or did not (SED, n=6) run on a motorized treadmill 6 × per week × 15–60‐min per session @ 10–20% grade × 12 weeks. SED mice maintained familiarity with treadmill‐running by completing 1 × 15‐min bout per week. Total work (kgm) performed during a maximal exercise test at 12‐weeks was greater (p<0.04) in ETR (2.29± 0.25) vs. SED (1.67± 0.15) mice. While body composition assessed via nuclear magnetic resonance was similar among SED mice before and after 12‐weeks, lean mass increased (p<0.03) and fat mass decreased (p<0.03) when pre to post NMR measures were compared within ETR animals. 24 h after the last bout of exercise, ECs and media + adventitia (M+A) were obtained from the iliac arteries of ETR and SED mice. mRNA expression was quantified by real‐time RT‐PCR using SYBR green fluorescence. Cycle threshold (Ct) values were normalized to the housekeeping gene 18S. Purity of the EC and M+A fractions obtained from the iliac artery was confirmed by measuring PECAM‐1 and ɑ‐SMA expression respectively. EC mRNA expression was greater (p<0.05) for beclin‐1, LC3‐II, Atg3, Atg5, and Atg7 in ETR vs. SED mice. Further, LC3II:GAPDH and LC3II:LC3I protein expression was greater (p<0.05) in aortic homogenates from ETR vs. SED mice. Intraluminal flow‐mediated vasodilation responses to ΔP of 6, 12, 18, 24, and 30 mmHg at 60 mmHg were greater (p<0.05), and vasorelaxation to 10−9 to 10−4 M acetylcholine was larger (p<0.05), in femoral arteries from ETR vs. SED mice. Responses to sodium nitroprusside were similar between groups using isobaric and isometric assessments of arterial function. Collectively, these findings indicate that exercise‐training attenuates endothelial dysfunction and repressed vascular autophagy associated with aging. Ongoing studies using tamoxifen‐inducible EC specific disruption of Atg3 or Atg16L1 will determine whether exercise‐induced improvements in arterial function are secondary to elevated vascular autophagy.

Support or Funding Information

Supported by funding from the NIH (1RO3 AGO52848‐01A1), AHA (16GRNT31050004; AWRP 17POST33670663), and the University of Utah Undergraduate Research Opportunities Program.

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.