LncRNA AFAP1-AS1 promotes M1 polarization of macrophages and osteogenic differentiation of valve interstitial cells.

Abstract

Little is known about the biological functions and underlying mechanisms of long non-coding RNA AFAP1-AS1 in degenerative calcified aortic valve disease (DCAVD). This study aims to explore whether AFAP1-AS1 regulates macrophage polarization in aortic valve calcification. Macrophage polarization and AFAP1-AS1 expression were detected in normal and calcified aortic valves of DCAVD patients. To explore the effect of AFAP1-AS1 on macrophage polarization, gain and loss of function were performed in THP-1 cells, and the percentage of M1 and M2 and the expressions of M1 and M2 markers were analyzed. Meanwhile, osteogenic differentiation was examined in valve interstitial cells (VICs). Compared with normal valves, there were more M1, less M2, and high AFAP1-AS1 expressions in calcified aortic valves, which may indicate a relationship between AFAP1-AS1 and macrophage polarization. AFAP1-AS1 overexpression promoted M1 polarization in lipopolysaccharide (LPS) and interferon gamma (IFN-γ)-treated THP-1 cells but inhibited M2 polarization, as well as augmented VIC osteogenic differentiation. On the contrary, the silence of AFAP1-AS1 could induce macrophage to M2-type and inhibit VIC osteogenic differentiation. These results elucidate that AFAP1-AS1 can promote M1 macrophages polarization to aggravate VIC osteogenic differentiation, playing a role in aortic valve calcification.