Endothelium‐specific disruption of IGF‐1 signaling impairs blood flow regulation in mice

Abstract

Circulating levels of IGF‐1 decline during aging in humans, which significantly increases the risk for cardiovascular diseases and promotes cerebromicrovascular impairment. To test the hypothesis that impaired IGF‐1 input to endothelial cells promote aging‐like microvascular dysfunction, we utilized a novel mouse model: Igfr1f/f VE‐Cadherin‐Cre mice. We found that endothelium‐dependent increases in cerebral blood flow in response to contralateral whisker stimulation (laser speckle contrast imaging) were attenuated in mice with endothelium‐specific disruption of IGF‐1 signaling. In control mice functional hyperemia was significantly decreased by pharmacological inhibition of NO synthesis (L‐NAME). In contrast, increases in cerebral blood flow in response to contralateral whisker stimulation were unaffected by L‐NAME in Igfr1f/f VE‐Cadherin‐Cre mice. Collectively, our findings support the concept that IGF‐1 signaling is essential for healthy cerebromicrovascular endothelial function and provide evidence that decreased IGF‐1 input to endothelial cells results in impaired NO mediation of functional hyperemia, which may contribute to cognitive decline associated with age‐related IGF‐1 deficiency.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.