Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1β and IL-6

Minghui Ou  ¹ , Chuntang Zhang  ² , Jing Chen  ¹ , Shibo Zhao  ¹ , Shichao Cui  ¹ , Jie Tu  ³ Affiliations

• PMID: 32712318
• PMCID: PMC7378273
• DOI: 10.1016/j.omtn.2020.05.022

Free PMC article

Abstract

Pulmonary arterial hypertension (PAH) is a fatal cardiovascular disease that could eventually result in right ventricular failure. Recently, the roles of microRNAs (miRNAs) in PAH have been highlighted. The present study aims to investigate the effects of miRNA (miR)-340-5p on PAH induced by acute pulmonary embolism (APE) and the underlying mechanisms. miR-340-5p was lowly expressed, whereas interleukin 1β (IL-1β) and IL-6 were highly expressed in plasma of APE-PAH patients as compared to normal human plasma. Subsequently, IL-1β and IL-6 were confirmed to be two target genes of miR-340-5p using a dual-luciferase reporter gene assay. By conducting overexpression and rescue experiments, overexpression of miR-340-5p was evidenced to inhibit proliferation and migration of pulmonary artery smooth muscle cells (PASMCs) and inflammation via reducing IL-1β and IL-6 levels. Meanwhile, miR-340-5p led to the blocked nuclear factor κB (NF-κB) pathway with reduced NF-κB p65, matrix metalloproteinase 2 (MMP2), and MMP9 expression in PASMCs. Finally, the ameliorative effect of miR-340-5p on pathological lesions was further verified in rat models of APE-PAH. Altogether, overexpressed miR-340-5p inhibited the inflammatory response, proliferation, and migration of PASMCs by downregulating IL-1β and IL-6, thereby suppressing the progression of APE-PAH. miR-340-5p therefore holds promise as an anti-inflammatory therapeutic target.

Keywords: acute pulmonary embolism; inflammatory response; interleukin-1β; interleukin-6; microRNA-340-5p; migration; proliferation; pulmonary arterial hypertension.