NCT04200560

Autophagy Maintains Vascular Function Through a Novel Glycolysis-linked Pathway Regulating eNOS

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 16 (actual)
• Sponsor: University of Utah · Academic / Other
• Sex: All
• Age: 18 Years – 90 Years
• Healthy volunteers: Accepted

Summary

Aging is inevitable and is the primary risk factor for developing cardiovascular disease. The molecular mechanisms that drive vascular dysfunction in the context of aging are incompletely understood. The overall hypothesis is that the age-related decline in endothelial cell (EC) autophagy leads to arterial dysfunction. This study will determine whether physiological shear-stress affects autophagosome formation and nitrous oxide (NO) generation in ECs.

Detailed description

It is hypothesized that genetic autophagy suppression prevents shear-stress induced purinergic signaling to endothelial nitrous oxide synthase (eNOS) and this pathway will be evaluated in primary arterial ECs obtained from older adult (\> 60 years) and adult (18-30 years) subjects before and following rhythmic handgrip exercise that elevates brachial artery shear-rate similarly in both groups. ECs will be used to quantify markers of EC autophagy, eNOS activation, and NO generation. The study will also determine whether exercise-training attenuates the aging-associated decline in EC autophagy, and whether intact autophagy is required for training-induced vascular improvements. To evaluate this potential, it will be determined whether one-limb rhythmic handgrip exercise training by older adult (\> 60 y) human subjects is sufficient to elevate basal and shear-induced EC autophagy initiation, eNOS activation, and NO generation vs. the contralateral sedentary limb. Results from this work have tremendous potential to reveal a new therapeutic target and approach for restoring / maintaining vascular function in the aging population.

Conditions

• Vascular Diseases

Interventions

Type	Name	Description
OTHER	Rhythmic Handgrip Exercise	60 minute rhythmic handgrip exercise
OTHER	Chronic Exercise Training	Handgrip exercise training consisting of three 60-minute training sessions per week for eight weeks.

Timeline

• Start date: 2018-07-01
• Primary completion: 2022-05-30
• Completion: 2022-05-30
• First posted: 2019-12-16
• Last updated: 2022-08-22

Locations

1 site across 1 country: United States