Miho Kanazashi

Protective effects of astaxanthin on capillary regression in atrophied soleus muscle of rats

The capillary regression in skeletal muscles associated with a chronic decrease in activity is related to a dysfunction of endocapillary cells induced by over‐expression of oxidative stress. We hypothesized that treatment with astaxanthin, an antioxidant, would attenuate the oxidative stress induced by decreased skeletal muscle use, and that this attenuation would prevent the associated capillary regression. The purpose of the present study was to investigate the antioxidant and preventive effects of astaxanthin on capillary regression in the soleus muscle during hindlimb unloading.

Amelioration of capillary regression and atrophy of the soleus muscle in hindlimb‐unloaded rats by astaxanthin supplementation and intermittent loading

What is the central question of this study? We asked whether the combination of astaxanthin supplementation and intermittent loading would attenuate both the muscle atrophy and the capillary regression associated with chronic unloading. What is the main finding and its importance? Intermittent loading alone attenuated atrophy of the soleus, while astaxanthin treatment alone maintained the capillary network in the soleus. The combination of these two interventions ameliorated both the muscle atrophy and the capillary regression induced by chronic unloading.

Low-intensity running exercise enhances the capillary volume and pro-angiogenic factors in the soleus muscle of type 2 diabetic rats

Introduction: We determined the effects of low‐intensity exercise on the three‐dimensional capillary structure and associated angiogenic factors in the soleus muscle of Goto‐Kakizaki (GK) diabetic rats. Methods: Four groups of male rats were studied: sedentary nondiabetic (Con), exercised nondiabetic control (Ex), sedentary GK, and exercised GK (GK+Ex). Rats in the Ex and GK+Ex groups were subjected to chronic low‐intensity running on a treadmill (15 m/min, 60 min/session, 5 sessions/week for 3 weeks). Results: Although mean capillary volume and diameter were lower in the GK compared with all other groups, low‐intensity exercise increased both of these measures in GK rats. Mitochondrial markers, i.e., SDH activity and PGC‐1α expression, and the levels of angiogenic factors were higher in the GK+Ex than all other groups. Exercise increased vascular endothelial growth factor (VEGF) protein levels and the VEGF‐to‐TSP‐1 ratio, an indicator of angiogenesis, in GK rats. Conclusions: Combined, the results indicate that low‐intensity exercise reduces some of the microcirculatory complications in type 2 diabetic muscles. Muscle Nerve 51: 391–399, 2015

Astaxanthin supplementation attenuates immobilization-induced skeletal muscle fibrosis via suppression of oxidative stress

Immobilization induces skeletal muscle fibrosis characterized by increasing collagen synthesis in the perimysium and endomysium. Transforming growth factor-β1 (TGF-β1) is associated with this lesion via promoting differentiation of fibroblasts into myofibroblasts. In addition, reactive oxygen species (ROS) are shown to mediate TGF-β1-induced fibrosis in tissues. These reports suggest the importance of ROS reduction for attenuating skeletal muscle fibrosis. Astaxanthin, a powerful antioxidant, has been shown to reduce ROS production in disused muscle. Therefore, we investigated the effects of astaxanthin supplementation on muscle fibrosis under immobilization. In the present study, immobilization increased the collagen fiber area, the expression levels of TGF-β1, α-smooth muscle actin, and superoxide dismutase-1 protein and ROS production. However, these changes induced by immobilization were attenuated by astaxanthin supplementation. These results indicate the effectiveness of astaxanthin supplementation on skeletal muscle fibrosis induced by ankle joint immobilization.

Abnormalities in three-dimensional capillary architecture and imbalance between vascular endothelial growth factor-A and thrombospondin-1 in soleus muscle of ovariectomized rat

Reduced ovarian hormone levels associated with menopause or ovariectomy (OVX) not only result in vascular dysfunction but also lead to structural abnormalities in capillaries. Therefore, the effect of OVX on the three-dimensional (3-D) architecture of capillary networks and the underlying molecular mechanisms were investigated in rat soleus muscle. Seven-week-old female Wistar rats were divided into the OVX and sham-treated (Sham) groups. The OVX group exhibited lower endurance exercise capacity compared to the sham group and resulted in decreased capillary diameter, number of anastomoses and capillary/anastomosis volume in soleus muscle, indicating 3-D structural abnormalities of capillary networks. Furthermore, OVX led to increased concentrations of thrombospondin-1 (TSP-1) protein and a decreased VEGF-A/TSP-1 ratio, an indicator of angio-adaptations, in soleus muscle compared with the Sham group. These results indicate OVX may induce 3-D capillary regression in soleus muscle through an imbalance between VEGF-A and TSP-1 expression, possibly associated with decreased exercise tolerance in ovariectomized rats.