Knockdown of H19 Attenuates Ox-LDL-induced Vascular Smooth Muscle Cell Proliferation, Migration, and Invasion by Regulating miR-599/PAPPA Axis.

Abstract

Long noncoding RNAs could participate in the development of atherosclerosis (AS). However, the underlying mechanism by which long noncoding RNA H19 is implicated in AS remains largely unknown. In this study, we investigated the function of H19 on cell proliferation, migration, and invasion in oxidized low-density lipoprotein (ox-LDL)-treated human aortic vascular smooth muscle cells (HA-VSMCs), and on hyperlipidemia response in high-fat diet (HFD)-treated ApoE-/- mice. Moreover, we explored the target interaction among H19, microRNA (miR)-599, and pappalysin 1 (PAPPA). Our results showed that H19 expression was elevated in serum samples of patients with AS and ox-LDL-treated HA-VSMC. H19 silence mitigated ox-LDL-induced proliferation, migration, and invasion of HA-VSMCs. H19 acted as a sponge for miR-599, and miR-599 knockdown reversed the suppressive effect of H19 silence on proliferation, migration, and invasion of HA-VSMCs. PAPPA was a target of miR-599 and attenuated the inhibitive role of miR-599 in HA-VSMC processes. H19 knockdown repressed PAPPA expression by increasing miR-599. Moreover, H19 interference alleviated hyperlipidemia response in HFD-treated ApoE-/- mice. Collectively, knockdown of H19 inhibited proliferation, migration, and invasion of ox-LDL-treated HA-VSMCs and hyperlipidemia response in HFD-treated ApoE-/- mice by regulating miR-599/PAPPA axis, indicating H19 might act as a potential target for the treatment of AS.