Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers

Abstract

Aging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial functionin both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and bloodbiomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-inducedrelaxations of the aorta were decreased in 3-, 6-, and 12-month-old rats compared to those in 1-month-old female rats. In males,maximum relaxations related to ACh were higher in 1- and 6-month-old rats than in 3- and 12-month-old rats. Plasma levels of nitricoxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAC) andhydrogen sulfide ($H_2S$) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAC, and ADMA decreased with age,and H$H_2S$ levels increased. Aging also caused a sex-dependent alteration in epigenetic modification of vessels. Expressions of H3K27me2,H3K27me3, H3K36me2, and H3K36me3 were much higher in vessels of 12-month-old female rats compared to those in younger agegroups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-relatedbiomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of thelife span.