Vasodilatory function in human skeletal muscle feed arteries with advancing age: the role of adropin

Key points

This study sought to determine the impact of aging on endogenous adropin levels in human skeletal muscle feed arteries (SMFAs) and the role of adropin in age‐related vascular dysfunction. Adropin protein expression falls progressively with advancing age in the human peripheral vasculature and endothelial‐dependent vasodilation, typically attenuated with age, was strongly correlated with SMFA adropin protein levels. Adropin incubation restored age‐related endothelial‐dependent vasodilatory dysfunction and increased p‐eNOS/eNOS ratio in an age‐dependent manner in the SMFAs. The role of NO bioavailability was additionally evidenced by NOS blockade ablating both the positive vascular effects of adropin incubation and the relationship between endothelial function and adropin protein expression. Additional evidence of a mechanistic link between declining adropin and age‐related endothelial dysfunction was documented by a progressively increasing magnitude of effect of adropin‐induced eNOS‐mediated vasodilation with aging. Adropin, appears to be a novel therapeutic target to facilitate the restoration of endothelial function with aging.

Abstract

This study sought to determine the impact of advancing age on endogenous adropin levels in human skeletal muscle feed arteries (SMFAs) and the role of adropin in age‐related vascular dysfunction. Adropin protein expression and vasodilatory capacity was assesed in SMFAs from Young (Y, 27 ± 2 yrs, n = 10), Middle aged (MA, 54 ± 2 yrs, n = 10), and Old (O, 75 ± 2 yrs, n = 16) subjects. Endothelial‐dependent vasodilation, with and without adropin incubation, was assessed in response to flow‐induced shear stress and acetylcholine (ACh). Both SMFA adropin protein expression and endothelial‐dependent vasodilatory function exhibited a progressive, age‐related, reduction (Flow: Y: 65 ± 3; MA: 36 ± 3; O: 15 ± 2%; ACh: Y: 63 ± 2, MA: 34 ± 3 %; O: 23 ± 3 %, P<0.05). There was a strong positive correlation between SMFA adropin protein expression and both flow‐ (r = 0.81, P<0.05) and ACh‐ (r = 0.78, P<0.05). Adropin incubation in the MA and O SMFAs restored the vasodilatory response to flow (MA+Adropin: 59 ± 3; O+Adropin: 47 ± 3 %, P<0.05) and ACh (MA+Adropin: 59 ± 3 %; O+Adropin: 49 ± 2 %, P<0.05). A mechanistic link between adropin and NO biovavailabilty was supported by 1) an increased phosphorylated eNOS/eNOS protein expression with adropin incubation only in the MA and O SMFAs, 2) eNOS blockade ablating both the positive vascular effects of adropin incubation and the relationship between endothelial function and adropin protein expression and, finally, 3) a progressive increase in the magnitude of effect of adropin‐induced eNOS‐mediated vasodilation with advancing age. Adropin could be a novel therapeutic target to facilitate the restoration of endothelial function, through increased NO bioavailability, with advancing age.

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