Abstract 14129: S18 Alleviates The Inflammatory Responses In Interstitial Cells Of Aortic Valves Through Up-regulation Interleukin 37

Abstract

Background: Calcific aortic valve disease (CAVD) is a common cardiovascular disease,which leads to the failure of valvular function in the elderly. CAVD is characterized by complex pathophysiological processes, including inflammation-induced osteoblastic differentiation of aortic valve interstitial cells (AVICs). Anti-CAVD agents with new mechanisms of action are urgently needed. S18 is obtained from a marine-derived Streptomyces strain, and it has a potent anti-inflammatory effect. However, its effect on CAVD is unknown. This study is sought to investigate the role of the natural product S18 in alleviating CAVD progression. Methods and Results: Human AVICs treated with LPS showed up-regulation of inflammatory factors ICAM-1, IL-8, and MCP-1, and significant calcification evaluated by Alizarin Red staining. S18 (2 μM) attenuated LPS-induced human AVICs inflammation. RNA-sequencing was used to identify differentially expressed genes (DEGs) in human AVICs treated with LPS or LPS + S18. Transcriptome data indicated the common DEGs enrichment in NF-κB pathway. Further, S18 inhibited phosphorylation of NF-κB induced by LPS. Previous studies suggested that IL-37 is a potential anti-inflammatory target of S18 in AVICs. Knockdown of IL-37 by siRNA exaggerated LPS-induced inflammation, and attenuated the anti-inflammatory effect of S18 on AVICs. Conclusion: Our results demonstrate that S18 attenuates LPS-mediated inflammation in human AVICs through inhibiting NF-κB activation, and underlying the mechanism of the anti-inflammatory effect involving up-regulation of IL-37. Our finding provides a novel avenue of preventing the progression of valve calcification.