Exercise, Vascular Stiffness, and Tissue Transglutaminase

Abstract

BackgroundVascular aging is closely associated with increased vascular stiffness. It has recently been demonstrated that decreased nitric oxide (NO)‐induced S‐nitrosylation of tissue transglutaminase (TG2) contributes to age‐related vascular stiffness. In the current study, we tested the hypothesis that exercise restores NO signaling and attenuates vascular stiffness by decreasing TG2 activity and cross‐linking in an aging rat model.Methods and ResultsRats were subjected to 12 weeks of moderate aerobic exercise. Aging was associated with diminished phosphorylated endothelial nitric oxide synthase and phosphorylated vasodilator‐stimulated phosphoprotein abundance, suggesting reduced NO signaling. TG2 cross‐linking activity was significantly increased in old animals, whereas TG2 abundance remained unchanged. These alterations were attenuated in the exercise cohort. Simultaneous measurement of blood pressure and pulse wave velocity (PWV) demonstrated increased aortic stiffness in old rats, compared to young, at all values of mean arterial pressure (MAP). The PWV‐MAP correlation in the old sedentary and old exercise cohorts was similar. Tensile testing of the vessels showed increased stiffness of the aorta in the old phenotype with a modest restoration of mechanical properties toward the young phenotype with exercise.ConclusionsIncreased vascular stiffness during aging is associated with decreased TG2 S‐nitrosylation, increased TG2 cross‐linking activity, and increased vascular stiffness likely the result of decreased NO bioavailability. In this study, a brief period of moderate aerobic exercise enhanced NO signaling, attenuated TG cross‐linking activity, and reduced ex vivo tensile properties, but failed to reverse functional vascular stiffness in vivo, as measured by PWV.

Effects of aging on liver microcirculatory function and sinusoidal phenotype

“…Male Wistar rats at the age of 20 months old were used to evaluate aging and compared to young animals of 3 months old ( n  = 12 animals per group) (Steppan et al, 2014; Wang, Wehling‐Henricks, Samengo, & Tidball, 2015). Animals were kept in environmentally controlled animal facilities at IDIBAPS.…”

Vascular ageing and endothelial cell senescence: Molecular mechanisms of physiology and diseases

“…Indeed, TG2 extracellular secretion and crosslinking activity are inhibited by S-nitrosylation, a post-translational modification of the cysteine residues in TG2 active site, by NO (Santhanam et al, 2010;Melino et al, 1997). Decreases in NO in arteria of old rats results to decreased TG2 S-nitrosylation, increased TG2 in the vascular matrix, and increased TG2 crosslinking function (Santhanam et al, 2010;Steppan et al, 2014).…”

Mechanical heterogeneities in the subendothelial matrix develop with age and decrease with exercise

“…The standard clinical methodology to measure vessel stiffness and predict CVD is pulse wave velocity (PWV) testing, which is typically performed using ultrasound (Kohn and Lampi et al ., 2015; Laurent et al , 2006; Mitchell et al , 2010; Van Bortel et al , 2012). PWV values have been shown to increase with age and decrease with exercise (Di Lascio et al , 2014; Gu et al , 2014a; Steppan et al , 2014). However, while PWV is important in the prediction of the development of CVD, it is an indirect measure of bulk vessel stiffness and many studies attribute bulk mechanical properties to the medial layer (Kohn and Lampi et al ., 2015; Shadwick, 1999).…”