The Klotho gene is a suppressor of the aging phenomena, and the secretion as well as the circulation of Klotho proteins decrease with aging. Although habitual exercise has antiaging effects (e.g., a decrease in arterial stiffness), the relationship between Klotho and habitual exercise remains unclear. In the present study, we investigated the effect of habitual exercise on Klotho, with a particular focus on arterial stiffness. First, we examined the correlation between plasma Klotho concentration and arterial stiffness (carotid artery compliance and β-stiffness index) or aerobic exercise capacity [oxygen uptake at ventilatory threshold (VT)] in 69 healthy, postmenopausal women (50–76 years old) by conducting a cross-sectional study. Second, we tested the effects of aerobic exercise training on plasma Klotho concentrations and arterial stiffness. A total of 19 healthy, postmenopausal women (50–76 years old) were divided into two groups: control group and exercise group. The exercise group completed 12 wk of moderate aerobic exercise training. In the cross-sectional study, plasma Klotho concentrations positively correlated with carotid artery compliance and VT and negatively correlated with the β-stiffness index. In the interventional study, aerobic exercise training increased plasma Klotho concentrations and carotid artery compliance and decreased the β-stiffness index. Moreover, the changes in plasma Klotho concentration and arterial stiffness were found to be correlated. These results suggest a possible role for secreted Klotho in the exercise-induced modulation of arterial stiffness.

Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, increase with advancing age and menopausal status. ADMA plays a role in endothelial dysfunction and increasing arterial stiffness. Regular aerobic exercise has a positive effect on arterial function (i.e., arterial compliance). This study investigated the effects of aerobic exercise training on plasma ADMA concentrations and arterial compliance in postmenopausal women. Thirty postmenopausal women were divided into 2 groups: an exercise group (n = 20) and a control group (n = 10). Subjects in the exercise group completed 12 weeks of aerobic exercise training (65%–80% of maximal heart rate, 40–60min/day, 3–6 days/week). Before and after each intervention, plasma ADMA concentrations and carotid arterial compliance were measured in all participants. The baseline plasma ADMA concentrations, carotid arterial compliance, and most other key dependent variables did not differ between the 2 groups. In the exercise group, carotid arterial compliance significantly increased after exercise intervention (P < 0.01), and plasma ADMA concentrations significantly decreased (P < 0.05). In addition, changes in carotid arterial compliance after the exercise intervention were inversely correlated with changes in plasma ADMA concentrations (r = −0.367; P < 0.05). We demonstrated that aerobic exercise training significantly decreased plasma ADMA concentrations with increase in carotid arterial compliance in postmenopausal women. These results suggest that reduction in ADMA may play an important role in the aerobic exercise training–induced increase in arterial compliance.

The capillary network is distributed throughout the body, and its reconstruction is induced under various pathophysiological conditions. MicroRNAs are small noncoding RNAs that regulate gene expression via posttranscriptional mechanisms and are involved in many biological functions, including angiogenesis. Previous studies have shown that each microRNA of miR-23 clusters, composed of the miR-23a cluster (miR-23a~27a~24-2) and miR-23b cluster (miR-23b~27b~24-1), regulates angiogenesis in vitro. However, the role of miR-23 clusters, located within a single transcription unit, in angiogenesis in vivo has not been elucidated. In the present study, we generated vascular endothelial cell (EC)-specific miR-23 cluster double-knockout (DKO) mice and demonstrated sprouting angiogenesis under various conditions, including voluntary running exercise, hindlimb ischemia, skin wound healing, and EC sprouting from aorta explants. Here, we demonstrated that EC-specific miR-23 DKO mice are viable and fertile, with no gross abnormalities observed in pups or adults. The capillary number was normally increased in the muscles of these DKO mice in response to 2 wk of voluntary running and hindlimb ischemia. Furthermore, we did not observe any abnormalities in skin wound closure or EC sprouting from aortic ring explants in EC-specific miR-23 cluster DKO mice. Our results suggest that endothelial miR-23 clusters are dispensable for embryonic development and postnatal angiogenesis in vivo. NEW & NOTEWORTHY We generated vascular endothelial cell (EC)-specific miR-23a/b cluster double-knockout mice and determined sprouting angiogenesis under various conditions, including voluntary running exercise, hindlimb ischemia, skin wound healing, and EC sprouting from aorta explants. We demonstrated that the double-knockout mice were viable and fertile, with no gross abnormalities in exercise- and ischemia-induced angiogenesis and skin wound closure or EC sprouting from aortic ring explants.