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Updated: Sep 27, 2025
08:44
Activating Autophagy by Aerobic Exercise in Mice
Published on: February 3, 2017
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Activating P2Y1 receptors improves function in arteries with repressed autophagy
Jae Min Cho1,2, Seul-Ki Park1,2, Oh Sung Kwon3,4
1Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, UT, USA.
Cardiovascular Research
|April 14, 2022
Summary
Endothelial cell autophagy is crucial for vascular health, declining with age. Activating P2Y1 receptors can restore arterial function in aged or impaired vessels, highlighting a therapeutic target.
Area of Science:
- Vascular Biology
- Cellular Autophagy
- Aging Research
Background:
- Endothelial cell (EC) autophagy is vital for vascular homeostasis.
- Previous work linked EC autophagy to nitric oxide (NO) generation via purinergic signaling.
- Age-related decline in EC autophagy impairs vascular function.
Purpose of the Study:
- To investigate the translational and functional significance of EC autophagy in aging.
- To determine if impaired EC autophagy contributes to age-associated arterial dysfunction.
- To explore P2Y1 receptor activation as a therapeutic strategy.
Main Methods:
- Assessed EC autophagy, p-eNOS(S1177) activation, and NO generation in adult vs. older humans and mice.
- Utilized exercise and shear stress models in vivo and in vitro.
- Employed pharmacological (3-MA) and genetic (iecAtg3KO) methods to impair autophagy.
- Investigated the role of purinergic 2Y1 receptors (P2Y1-R) in flow-mediated vasodilation.
Main Results:
- Older humans and mice showed blunted EC autophagy and impaired arterial function compared to adults.
- Shear stress induced autophagy, glycolysis, and NO generation in adult ECs, but not older ECs.
- Arterial dysfunction in aged or autophagy-impaired adult mice was recapitulated by NO synthase inhibition, autophagy impairment, or P2Y1-R blockade.
- P2Y1-R activation improved vasodilation in impaired adult and older mouse arteries.
Conclusions:
- Age-associated decline in EC autophagy contributes to arterial dysfunction.
- P2Y1 receptor activation can restore vascular function in conditions of compromised EC autophagy.
- Targeting P2Y1 receptors offers a potential therapeutic approach for age-related vascular impairment.
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