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High-intensity interval training modulates retinal microvascular phenotype and DNA methylation of p66Shc gene: a randomized controlled trial (EXAMIN AGE)

Streese, Lukas and Khan, Abdul Waheed and Deiseroth, Arne and Hussain, Shafaat and Suades, Rosa and Tiaden, Andre and Kyburz, Diego and Cosentino, Francesco and Hanssen, Henner. (2019) High-intensity interval training modulates retinal microvascular phenotype and DNA methylation of p66Shc gene: a randomized controlled trial (EXAMIN AGE). European Heart Journal, 41 (15). pp. 1514-1519.

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Official URL: https://edoc.unibas.ch/71489/

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Abstract

Impairments of retinal vessel diameter are associated with major adverse cardiovascular (CV) events. Promoter DNA methylation is a repressor of the mitochondrial adaptor p66Shc gene transcription, a key driver of ageing-induced reactive oxygen species. The study aimed to investigate whether high-intensity interval training (HIIT) affects retinal microvascular phenotype as well as p66Shc expression and oxidative stress in ageing subjects with increased CV risk from the EXAMIN AGE cohort.; Eighty-four sedentary subjects (mean age 59.4 ± 7.0 years) with ≥2 CV risk factors were randomized into either a 12-week HIIT or standard physical activity recommendations. Retinal arteriolar and venular diameters were measured by use of a retinal vessel analyser. As a marker of oxidative stress plasma 3-nitrotyrosine (3-NT) level was determined by ELISA. Gene expression of p66Shc and DNA methylation were assessed in mononuclear cells by RT-qPCR and methylated-DNA capture (MethylMiner Enrichment Kit) coupled with qPCR, respectively. High-intensity interval training reduced body mass index, fat mass, low-density lipoprotein and increased muscle mass, as well as maximal oxygen uptake (VO2max). Moreover, HIIT restored microvascular phenotype by inducing retinal arteriolar widening (pre: 175 ± 14 µm vs. post: 181 ± 13 µm, P = 0.001) and venular narrowing (pre: 222 ± 14 µm vs. post: 220 ± 14 µm, P = 0.007). After HIIT, restoration of p66Shc promoter methylation (P = 0.034) reduced p66Shc gene expression (P = 0.037) and, in turn, blunted 3-NT plasma levels (P = 0.002).; High-intensity interval training rescues microvascular dysfunction in ageing subjects at increased CV risk. Exercise-induced reprogramming of DNA methylation of p66Shc gene may represent a putative mechanistic link whereby exercise protects against age-related oxidative stress.; ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976).
Faculties and Departments:03 Faculty of Medicine > Departement Sport, Bewegung und Gesundheit > Bereich Sport- und Bewegungsmedizin > Präventive Sportmedizin (Hanssen)
UniBasel Contributors:Streese, Lukas
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Oxford University Press
ISSN:0195-668X
e-ISSN:1522-9645
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:08 Jul 2020 13:00
Deposited On:08 Jul 2020 13:00

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