Lithium chloride (LiCl), a pharmacological compound, was effective in reducing
inflammation, but whether it can protect against
abdominal aortic aneurysm (AAA) is largely unknown. This study is designed to investigate
therapeutic effects of LiCl on AAA and the potential mechanism. Rat AAA models were induced by periaortic application of CaCl2. AAA rats were treated by daily
intraperitoneal injection of LiCl or vehicle alone to study the protection effects of LiCl in vivo. Rat primary vascular smooth muscle cells (VSMCs) stimulated with
tumor necrosis factor (TNF)-α served as an in vitro model. LiCl treatment prevented the development of AAA through inhibiting the inflammatory cells infiltration and inflammatory
cytokines overproduction, as well as attenuating
superoxide production and
elastin degradation in aorta of AAA rats. Additionally, the downregulation of p-GSK3β(Ser9) and
SIRT1, upregulation of NF-κB(p-65), MMP-2 and MMP-9 in AAA were abolished by LiCl treatment. In vitro by upregulating p-GSK3β(Ser9), LiCl significantly induced
SIRT1 expression, along with inhibition of the NF-κB activation and decreased
elastin level elicited in VSMCs by TNF-α stimulation.
SIRT1 activator
SRT1720 achieved similar repressive effects as LiCl on TNF-α-induced NF-κB activation and decreased
elastin in VSMCs. Moreover, administration of LiCl also caused regression of established rats AAA. This study provided the first evidence that LiCl prevented the development of AAA through inhibiting
inflammation,
MMPs, and
superoxide production, and facilitating the biosynthesis of
elastin. The beneficial effect of LiCl may be mediated by regulation GSK3β/
SIRT1/NF-κB cascade.