Furthermore, the in vivo results showed that Met not only significantly the inhibited HHcy-induced upregulation of endothelin receptors and acetylated p65 but also recovered the HHcy-induced decrease in Sirt1 in a dosage-dependent manner in SMA.
In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX-1 expression, subsequently causing reactive oxygen species generation, up-regulation of NADPH oxidase activity and NF-κB activation, thereby promoting pro-inflammatory response and cell apoptosis.
In the animal model of diet-induced hyperhomocysteinemia (HHcy), we observed the similar findings that SIRT1/PGC-1α/PPAR-γ cascades were downregulated with elevated MMP-13 and COX-2.