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

NCT04200560 | Completed

• 1 other identifier: 00077971
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Vascular Diseases

Keywords

Aging; Endothelial Cell Autophagy

Outcome Measures

Primary Outcomes (14)

• Change in biomarker beclin-1 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker Atg3 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker Atg5 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker Atg7 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker Lamp1 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker Lamp2 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker p62 after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker beclin-1 after chronic exercise training

  8 weeks

• Change in biomarker Atg3 after chronic exercise training

  8 weeks

• Change in biomarker Atg5 after chronic exercise training

  8 weeks

• Change in biomarker Atg7 after chronic exercise training

  8 weeks

• Change in biomarker Lamp1 after chronic exercise training

  8 weeks

• Change in biomarker Lamp2 after chronic exercise training

  8 weeks

• Change in biomarker p62 after chronic exercise training

  8 weeks

Secondary Outcomes (6)

• Change in radial arterial diameter after Rhythmic Handgrip Exercise

  60 min

• Change in radial arterial flow rate after Rhythmic Handgrip Exercise

  60 min

• Change in biomarker p-eNOSS1177 after Rhythmic Handgrip Exercise

  60 min

• Change in radial arterial diameter after chronic exercise training

  8 weeks

• Change in radial arterial flow rate after chronic exercise training

  8 weeks

Study Arms (2)

Healthy Adult Subjects

EXPERIMENTAL

Healthy adult subjects (18 - 30 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise

Other: Rhythmic Handgrip Exercise

Healthy Older Adult Subjects

EXPERIMENTAL

Healthy older adult subjects (\> 60 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise and after Chronic Exercise Training.

Other: Rhythmic Handgrip Exercise; Other: Chronic Exercise Training

Interventions

Rhythmic Handgrip Exercise OTHER

60 minute rhythmic handgrip exercise

Healthy Adult Subjects; Healthy Older Adult Subjects

Chronic Exercise Training OTHER

Handgrip exercise training consisting of three 60-minute training sessions per week for eight weeks.

Healthy Older Adult Subjects

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Candidates must be between 18 and 90 y of age
• Candidates must be free of overt disease as assessed by a) medical history; b) standard blood chemistries (chem. 7 panel), c) ECG at rest; d) limb vascular examination (ankle-brachial BP index \> 0.9); e) resting BP \< 140/90 mmHg; and f) skinfold % body fat assessment.
• Subjects will have a body mass index (BMI) between 19 and 30 and have plasma glucose concentrations \< 7.0 mmol/L under fasting conditions and \< 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)

You may not qualify if:

• Candidates \<18 or \>90 y of age
• Candidates demonstrating abnormal ECG, ankle-brachial BP index \<0.9, resting BP \> 140/90
• Candidates demonstrating a BMI \<19 or \> 30
• Candidates demonstrating plasma glucose concentrations \> 7.0 mmol/L under fasting conditions and \> 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
• Candidates demonstrating dyslipidemia (plasma total cholesterol \> 240 mg/dl with LDL-cholesterol \> 160 mg/dl)
• Candidates reporting a history of myocardial infarction, unstable cardiac ischemia, recent cardiac catheterization, carotid artery disease, transient ischemic attack
• Women taking hormone replacement therapy (HRT) currently or in the preceding year will be excluded from the proposed studies due to the direct vascular effects of HRT.

Sponsors & Collaborators

• University of Utah: lead

Study Sites (1)

VA Medical Center

Salt Lake City, Utah, 84148, United States

Location

MeSH Terms

Conditions

Vascular Diseases

Condition Hierarchy (Ancestors)

Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: December 16, 2019
• Study Start: July 1, 2018
• Primary Completion: May 30, 2022
• Study Completion: May 30, 2022
• Last Updated: August 22, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)