BubR1 insufficiency impairs angiogenesis in aging and in experimental critical limb ischemic mice

Aging impairs angiogenesis, mediates endothelial dysfunction, and leads to increased prevalence of both cardiovascular disease and adverse sequelae in the elderly. These pathologies lead to higher mortality and an elevated risk of limb amputation. BubR1, a cell cycle-related protein, is a crucial factor in aging. This study presents novel findings indicating that BubR1 insufficiency impairs angiogenesis and results in limb amputation in the critical limb ischemic mouse model. We also showed that the decrease in BubR1 expression was associated with a reduction in vascular endothelial growth factor expression and hypoxia inducible factor-1α instability. Therefore, BubR1 insufficiency delayed angiogenesis, which eventually resulted in limb loss.