Abstract P3059: Hydrogen Sulfide Inhibits Aortic Valve Fibrosis, Inflammation And Calcification By Inducing Pro-autophagy Effect In Human Valvular Interstitial Cells

Abstract

Background: As of now, there is no pharmacological treatment for aortic valve stenosis (AS) except for valve replacement. In the previously studied proteomics analysis, we demonstrated that the expression of sulfide:quinone oxidoreductase (SQOR) was significantly lower in aortic valve interstitial cells (VICs) isolated from AS patients than those of normal patients. However, the role of SQOR in AS pathophysiology has not been clarified yet. Methods: To elucidate the cellular mechanism of SQOR and hydrogen sulfide (H2S) as therapeutic aspects in AS, we studied the effects of NaHS (H2S-releasing compound) on diseased aortic VICs using real-time PCR and western blots. Results: NaHS treatment led to increased SQOR expression in diseased aortic VICs and induced an increase of the Nrf2-target genes, especially NQO1. It showed that the effects of NaHS decreased not only fibrosis and inflammation markers (MMP9, TNF-α, IL6) but also calcification markers (ALP, osteocalcin, RUNX2, COL1A1). In addition, AMPK and Beclin-1 significantly increased by NaHS while Akt and mTOR decreased which is expected to have pro-autophagy effect. Conclusion: H2S releasing compound enhances the expression of SQOR and activates AMPK/mTOR mediated pro-autophagy function resulting in inhibition of fibrosis, inflammation and calcification in human VICs. Therefore, H2S can be a potential therapeutic target in AS.