Figure 7.

Mechanisms of leucine in the protection of aging-induced vascular remodeling. Transport of leucine depends on amino acid transporters Slc7a5 and Slc3a2. Intracellular leucine increases protein level of Sirt1, which subsequently induces Sirt1-mediated Foxo1 deacetylation. Foxo1 deacetylation enhances Foxo1 activity in nucleus, which represses VSMC transition to a synthetic phenotype, vascular inflammatory responses, and excessive ROS generation. Meanwhile, leucine or Sirt1 may also relieve vascular inflammation and ROS level via Foxo1-independent mechanisms. Dietary leucine supplementation at middle-age stage reversed aging-induced vascular remodeling and dysfunction.