AgeR deletion decreases soluble fms-like tyrosine kinase 1 production and improves post-ischemic angiogenesis in uremic mice.

Peripheral arterial disease occurs more frequently and has a worse prognosis in patients with chronic kidney disease (CKD). The receptor for advanced glycation end products (RAGE) is involved in multiple aspects of uremia-associated vasculopathy. Previous data suggest that the RAGE pathway may promote soluble fms-like tyrosine kinase 1 (sFlt1) production, an anti-angiogenic molecule. Thus, we tested the hypothesis that the deletion of AgeR would decrease sFlt1 production and improve post-ischemic revascularization in uremic condition. We used a well-established CKD model (5/6 nephrectomy) in WT and AgeR-/- C57/Bl6 mice. Hindlimb ischemia was induced by femoral artery ligation. Revascularization was evaluated by complementary approaches: ischemic limb retraction, LASCA imagery, and capillary density. The production of sFlt1 was assessed at both RNA and protein levels. After hindlimb ischemia, uremic mice showed slower functional recovery (p < 0.01), decreased reperfusion (p < 0.01), lower capillary density (p = 0.02), and increased circulating sFlt1 levels (p = 0.03). AgeR deletion restored post-ischemic angiogenesis and was protective from sFlt1 increase in uremic mice. These findings show the main role of RAGE in post-ischemic angiogenesis impairment associated with CKD. RAGE may represent a key target for building new therapeutic approaches to improve the outcome of CKD patients with PAD.

Morphometric Analysis of the Umbilicus According to Age.

BACKGROUND: Morphometric and anatomical analyses of the shape and position of the umbilicus have been conducted in adults, but umbilicoplasty in children remains challenging because growth is still occurring. OBJECTIVES: The main objective of this study was to evaluate the difference in the position and shape of the umbilicus between childhood and adulthood. The secondary objective was to improve the surgical management of umbilicoplasty in children. METHODS: This prospective single-center study focused on the morphometric analysis of the umbilicus in 200 adults and children. All data, including standardized measures and pictures, were determined by one single operator. RESULTS: Despite a variation of approximately 2% in the xiphoid-pubis distance, the location of the umbilicus remains stable during the entire growth period. In a supine individual, the location is at one half to two thirds of the xiphoid-pubis distance (slightly lower in children), with a mean ratio of 0.57 for the xiphoid-umbilicus distance to the xiphoid-pubis distance. In the general population, the most common shapes are round and vertical oval. T-shaped umbilici were only observed in adults. Round and protruding shapes were twice as frequent in children under 18 as in adults. The horizontal oval shape was twice as frequent in adults. CONCLUSIONS: Abdominal growth and changes in the repartition of subcutaneous adipose tissues with age are responsible for the vertical orientation and deepening of the umbilicus as well as its horizontal orientation. To promote final cosmetic outcomes, secondary umbilicoplasty must place the umbilicus between one half and two thirds of the xiphoid-pubis distance.