This study investigated the regulatory role of long non-coding RNA (lncRNA) MALAT1 in HA-VSMCs prolifera-tion and apoptosis through mediating PTEN level. HA-VSMCs were induced with different doses of ox-LDL for various time points, and the relative level of MALAT1 was determined. MALAT1 was upregulated in a time-and dose-dependent manner. Overexpression of MALAT1 increased viability and proliferative rate, and decreased apoptotic rate of HA-VSMCs induced with 100 mg/L ox-LDL for 24 h, which was reversed by si-MALAT1 trans-fection. PTEN protein level was downregulated by ox-LDL induction and upregulated by si-MALAT1. MALAT1 was mainly distributed in the nucleus, and it interacted with EZH2. Silencing of MALAT1 attenuated EZH2 bind-ing on PTEN promoter region. Knockdown of PTEN reversed the decreased proliferative ability and increased apoptotic rate in ox-LDL-induced HA-VSMCs transfected with s-MALAT1. These results indicate that MALAT1 IP: 203.8.109.20 On: Wed, 02 Aug 2023 05:50:46 Copyright: American Scientific Publishers accelerates HA-VSMCs proliferation by recruiting EZH2 to mdite PTEN level. Overall, MALAT1 may play a Delivered by Ingenta crucial role in the progression of atherosclerosis and may be a potential therapeutic target.