Age- and sex-dependent alteration of functions and epigenetic modifications of vessel and endothelium related biomarkers
Aging is a main risk factor for development of cardiovascular diseases associated with the impairment of endothelial function
in both sexes. In the present study, age-related changes in vascular responsiveness, epigenetic modifications of vessel wall, and blood
biomarkers related to endothelial functions were examined in an age- and sex-dependent manner. Acetylcholine (ACh)-induced
relaxations 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 nitric
oxide (NO) and asymmetric dimethylarginine (ADMA) decreased with age in female rats, and total antioxidant capacity (TAC) and
hydrogen sulfide (H2S) levels displayed biphasic alterations. In male rats, plasma levels of NO, TAC, and ADMA decreased with age,
and H2S 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 age
groups. These results indicate that vascular functions, epigenetic modifications of vessels, and plasma levels of endothelium-related
biomarkers are affected by age and sex. These findings could be important for the assessment of vascular status over the course of the
life span.
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