About 230 million people worldwide suffer from peripheral arterial disease (PAD), and the prevalence is increasing year by year. Multiple risk factors, including smoking, dyslipidemia, diabetes, and hypertension, can contribute to the development of PAD. PAD is typically characterized by intermittent claudication and resting pain, and there is a risk of severe limb ischemia, leading to major adverse limb events, such as amputation. Currently, a major progress in the research field of the pathogenesis of vascular remodeling, including atherosclerosis and neointima hyperplasia has been made. For example, the molecular mechanisms of endothelial dysfunction and smooth muscle phenotype switching have been described. Interestingly, a series of focused studies on fibroblasts of the vessel wall has demonstrated their impact on smooth muscle proliferation and even endothelial function via cell-cell communications. In this review, we aim to focus on the functional changes of peripheral arterial cells and the mechanisms of the pathogenesis of PAD. At the same time, we summarize the progress of the current clinical treatment and potential therapeutic methods for PAD and shine a light on future perspectives.

Introduction: In this study, we investigated the role of the long non-coding RNA GAPLINC in atherosclerosis under oxidized low-density lipoprotein (ox-LDL) treatment.Material and methods: We utilized ox-LDL exposed human aortic endothelial cells as an in-vitro model. The expression level of GAPLINC was quantified by qPCR in different times and concentrations of ox-LDL treatment conditions. Cell apoptosis rate and cell cycle profiles were assessed by flow cytometry and TUNEL assay. The target association was confirmed using a luciferase reporter assay and Western blot.Results: We found that GAPLINC expression was induced by ox-LDL treatment, but cell proliferation ability was significantly inhibited. We further confirmed that overexpressing of lncRNA GAPLINC in ox-LDL-exposed HAECs decreased cell proliferation by increasing cell apoptosis and arresting cell cycle in G2/M and S phase. Importantly, the detailed mechanistic analysis elucidated that LncRNA GAPLINC acts as a decoy to sequester miR-183-5p to prevent it from binding to target PDCD4. MiR-183-5p targets GAPLINC, and PDCD4 is a downstream target of miR-183-5p, and the cellular effects of this direct interaction were confirmed by a rescue assay experiment.Conclusions: The present study demonstrates that upregulation of lncRNA GAPLINC represses the binding of miR-183-5p to the PDCD4 promoter region and then promotes PDCD4 expression, thereby inducing cell apoptosis and suppressing endothelial cell proliferation.