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High-intensity interval training improves cerebrovascular endothelial function and modulates p66Shc gene expression in cardiovascular risk patients: a randomized controlled trial

Session Poster Session 2

Speaker Lukas Streese

Event : ESC Preventive Cardiology (Formerly EuroPrevent) 2019

  • Topic : preventive cardiology
  • Sub-topic : Physical Inactivity and Exercise
  • Session type : Poster Session

Authors : L Streese (Basel,CH), AW Khan (Stockholm,SE), A Deiseroth (Basel,CH), S Hussain (Stockholm,SE), R Suades (Stockholm,SE), F Cosentino (Stockholm,SE), H Hanssen (Basel,CH)

L Streese1 , AW Khan2 , A Deiseroth1 , S Hussain2 , R Suades2 , F Cosentino2 , H Hanssen1 , 1University of Basel, Department of Sport, Exercise and Health, University of Basel - Basel - Switzerland , 2Karolinska Institute, Cardiology Unit, Department of Medicine Solna - Stockholm - Sweden ,



Endothelial dysfunction determines cardiovascular (CV) disease progression and vascular aging. Retinal vessels are part of the cerebrovascular bed and flicker-light induced retinal endothelial dilatation is a new diagnostic tool for CV risk assessment. The mitochondrial adaptor p66Shc is a known modulator of vascular aging and oxidative stress. The role of exercise as a determinant of cerebrovascular endothelial function and regulator of p66Shc expression has not been examined to date.


The study aimed to investigate the effects of exercise on retinal endothelial function as well as the regulation of p66Shc gene expression and oxidative stress in older patients with CV risk.


Eighty-four older and previously sedentary CV risk patients (aged 58±6 years) were randomized into a 12-week high-intensity interval training (HIIT) or control group (CG). Retinal endothelial function was measured by flicker light-induced maximal arteriolar (ADmax) dilatation as well as area under the arteriolar flicker curve (AFarea) using a retinal vessel analyzer. Plasma 3-nitrotyrosine (3-NT) was measured by ELISA as a marker of oxidative stress. Gene expression of p66Shc and DNA methylation were assessed in mononuclear cells by RT-qPCR and Methylminer qPCR. Microvascular and circulating biomarkers as well as maximal oxygen uptake (VO2max) were assessed before and after HIIT.


Both ADmax (p=0.018) and AFarea (p=0.016) increased significantly after HIIT compared to CG. There was a significant association between ? change VO2max and ? change ADmax and AFarea (R2=0.073, p=0.026; R2=0.08, p=0.019, respectively). HIIT increased methylation status of p66shc promoter and induced a downregulation of p66Shc expression, which was associated with lower 3-NT levels.


This is the first intervention trial to demonstrate that exercise has the potential to reverse cerebrovascular endothelial dysfunction in patients with CV risk. Dynamic retinal vessel analysis seems to be a valid diagnostic tool to detect treatment effects of exercise in the microvasculature. Exercise-induced reprogramming of DNA methylation on p66Shc gene promoter may represent a putative mechanistic link whereby exercise protects against age-related oxidative stress.

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