The proliferation and migration of vascular smooth muscle cells (VSMCs) is one of main reasons of vascular remodeling and is the pathogenesis of atherosclerosis and other vascular diseases. Transient receptor potential vanilloid 1 (TRPV1) is the specific receptor of capsaicin. TRPV1 has been previously reported to inhibit proliferation, migration and phenotypic switching, but the regulatory mechanisms and relevant signalling pathways are not clear. The aim of this study was to investigate the effects of capsaicin-activated TRPV1 on VSMC phenotypic switching. In this study, oxidized low density lipoprotein (ox-LDL) was used to induce the proliferation and migration of VSMCs. Our data showed that the VSMC proliferation induced by ox-LDL was dependent on the concentration of ox-LDL. Nevertheless, the data showed that capsaicin activated TRPV1 significantly decreased ox-LDL-induced superoxide anion generation. Phenotypic switching of VSMCs was inhibited by the activation of TRPV1. Furthermore, capsaicin decreased ox-LDL-induced superoxide anion generation by activating peroxisome proliferator activated receptor a (PPARa). TRPV1 inhibited VSMC phenotypic switching via upregulated expression of PPARa. It may be considered a useful target for the treatment of vascular remodeling. (c) 2021 Elsevier Inc. All rights reserved.