Abstract
Aim: The aim was to determine the role of aging and exercise training on endothelial mechanosensor proteins and the hyperemic response to shear stress by passive leg movement.Methods: We examined the expression of mechanosensor proteins and vascular function in young (n = 14, 25 ± 3 years) and old (n = 14, 72 ± 5 years) healthy male subjects with eight weeks of aerobic exercise training. Before and after training, the hyperaemic response to passive leg movement was determined and a thigh muscle biopsy was obtained before and after passive leg movement to assess the acute effect of increased shear stress. Biopsies were analyzed for protein amount and phosphorylation of mechanosensor proteins; Platelet endothelial cell adhesion molecule-1 (PECAM-1), Vascular endothelial cadherin, Vascular endothelial growth factor receptor-2 and endothelial nitric oxide synthase (eNOS).Results: Before training, the old group presented a lower hyperaemic response to passive leg movement and a 35% lower (P < 0.05) relative basal phosphorylation level of PECAM-1 whereas there was no difference for the other mechanosensor proteins. After training, the eNOS protein amount, the amount of PECAM-1 protein and the passive leg movement-induced phosphorylation of PECAM-1 were higher in both groups. The hyperaemic response to passive leg movement was higher after training in the young group only.Conclusion: Aged individuals have a lower hyperaemic response to passive leg movement and a lower relative basal phosphorylation of PECAM-1 than young. The higher PECAM-1 phosphorylation despite a similar hyperemic level in the aged observed after training, suggests that training improved shear stress responsiveness of this mechanotransduction protein.
Highlights
Impaired vascular function is a hallmark of aging (Seals et al, 2011) and vascular dysfunction is a strong predictor of cardiovascular disease (Widlansky et al, 2003; Deanfield et al, 2007; Green et al, 2011)
We have recently found that vascular function, assessed in vivo by passive leg movement, and alterations in the mechanosensor complex, can be impaired in young healthy subjects by two weeks of high sugar intake (Gliemann et al, 2017)
The principal findings are: (I) before training, compared to the young group, the older group presented a lower hyperaemic response to increased shear stress induced by passive leg movement, which was accompanied by a lower basal relative phosphorylation status of the endothelial mechanosensor platelet endothelial cell adhesion molecule (PECAM-1); (II) eight weeks of exercise training resulted in a higher PECAM-1 protein level and an enhanced passive leg movement induced phosphorylation of PECAM-1 in both the young and the older subjects; (III) exercise training resulted in a higher expression of endothelial nitric oxide synthase (eNOS) and a greater total eNOS phosphorylation in both young and aged individuals; (IV) after training, the hyperemic response to passive leg movement was higher in the young subjects
Summary
Impaired vascular function is a hallmark of aging (Seals et al, 2011) and vascular dysfunction is a strong predictor of cardiovascular disease (Widlansky et al, 2003; Deanfield et al, 2007; Green et al, 2011). Shear stress induces phosphorylation of vascular VEGFR2, vascular endothelial cadherin (VE-cadherin) and PECAM1 (Osawa et al, 2002; Shay-Salit et al, 2002; Tzima et al, 2005) which in turn causes phosphorylation and activation of eNOS (Fleming and Busse, 1999; Jin et al, 2003; Fleming et al, 2005; Tzima et al, 2005) Of these mechanosensor proteins, PECAM-1 has consistently been shown to be very important for endothelial cell function (Privratsky and Newman, 2014) but evidence for how mechanosensor proteins are influenced in humans is lacking. Studies on young subjects and older adults have shown that the hyperaemic response to passive leg movement is dependent on NO in both young and older subjects but that the hyperaemic response is reduced with aging (Mortensen et al, 2012; Trinity et al, 2015)
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