High-intensity interval training modulates retinal microvascular phenotype and DNA methylation of p66Shc gene: a randomized controlled trial (EXAMIN AGE). (16th April 2019)

• Record Type: Journal Article
• Authors: Streese, Lukas; Khan, Abdul Waheed; Deiseroth, Arne; Hussain, Shafaat; Suades, Rosa; Tiaden, Andre; Kyburz, Diego; Cosentino, Francesco; Hanssen, Henner
• Is Part Of: European heart journal. Volume 41:Number 15(2020)
• Page Start: 1514
• Page End: 1519
• Publication Date: 2019-04-16
• Subjects: Ageing -- Retinal microcirculation -- Oxidative stress -- p66Shc gene -- DNA methylation -- Exercise; Cardiology -- Periodicals; Heart -- Diseases -- Periodicals; 616.12005
• DOI: 10.1093/eurheartj/ehz196
• Languages: English
• ISSNs: 0195-668X

Abstract

Abstract: Aims: Impairments of retinal vessel diameter are associated with major adverse cardiovascular (CV) events. Promoter DNA methylation is a repressor of the mitochondrial adaptor p66 Shc 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 p66 Shc expression and oxidative stress in ageing subjects with increased CV risk from the EXAMIN AGE cohort. Methods and results: 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 p66 Shc 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 (VO2 max). 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 p66 Shc promoter methylation ( P = 0.034) reduced p66 Shc gene expression ( P = 0.037) and, in turn, blunted 3-NT plasma levels ( P = 0.002). Conclusion: High-intensity interval training rescues microvascular dysfunction in ageing subjects at increased CV risk. Exercise-induced reprogramming of DNA methylation of p66 Shc gene may represent a putative mechanistic link whereby exercise protects against age-related oxidative stress. Clinical trial registration: ClinicalTrials.gov: NCT02796976 (https://clinicaltrials.gov/ct2/show/NCT02796976 ).