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The mitochondrial integrity and function in endothelial cells are essential for angiogenesis. TIMM44 (translocase of inner mitochondrial membrane 44) is essential for integrity and function of mitochondria. Here we explored the potential function and the possible mechanisms of TIMM44 in angiogenesis. In HUVECs, human retinal microvascular endothelial cells and hCMEC/D3 brain endothelial cells, silence of TIMM44 by targeted shRNA largely inhibited cell proliferation, migration and in vitro capillary tube formation. TIMM44 silencing disrupted mitochondrial functions in endothelial cells, causing mitochondrial protein input arrest, ATP reduction, ROS production, and mitochondrial depolarization, and leading to apoptosis activation. TIMM44 knockout, by Cas9-sgRNA strategy, also disrupted mitochondrial functions and inhibited endothelial cell proliferation, migration and in vitro capillary tube formation. Moreover, treatment with MB-10 (“MitoBloCK-10”), a TIMM44 blocker, similarly induced mitochondrial dysfunction and suppressed angiogenic activity in endothelial cells. Contrarily, ectopic overexpression of TIMM44 increased ATP contents and augmented endothelial cell proliferation, migration and in vitro capillary tube formation. In adult mouse retinas, endothelial knockdown of TIMM44, by intravitreous injection of endothelial specific TIMM44 shRNA adenovirus, inhibited retinal angiogenesis, causing vascular leakage, acellular capillary growth, and retinal ganglion cells degeneration. Significant oxidative stress was detected in TIMM44-silenced retinal tissues. Moreover, intravitreous injection of MB-10 similarly induced oxidative injury and inhibited retinal angiogenesis in vivo. Together, the mitochondrial protein TIMM44 is important for angiogenesis in vitro and in vivo, representing as a novel and promising therapeutic target of diseases with abnormal angiogenesis.

Background Short stature is defined as height below 2 standard deviations of the population with the same age, gender. This study is aimed to assess the characteristics of body composition in preschool children with short stature. Methods Anthropometric measurements and body composition were assessed in 68 preschool children aged 3 to 6 years old with short stature and 68 normal controls matched on age and gender. Height, weight and body composition (total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents) in the two groups were measured and compared. Results The total body water, protein, minerals, body fat mass, fat-free mass, soft lean mass, skeletal muscle mass, and bone mineral contents were lower in preschool children with short stature than controls (P P = 0.03). Linear regression analysis showed that there was a positive correlation between height and fat-free mass index [β, 1.99 (0.59, 3.39), P = 0.01], a negative correlation between height and body fat percentage [β, − 0.20 (− 0.38, − 0.01), P = 0.04]. The proportions of fat-free mass in the upper limbs were significantly lower (Right,t = − 2.78,Left t = − 2.76, P Conclusions The fat-free mass such as protein and bone minerals is lower in preschool children with short stature, suggesting the monitoring of fat-free mass for early identification and intervention.