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

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.

Epigenetic Regulation of Pulmonary Arterial Hypertension-Induced Vascular and Right Ventricular Remodeling: New Opportunities?

“…In ECs, the miR-17~92 cluster and miR-27a are upregulated but miR-21, miR-424 and miR-503 are downregulated. miR-340-5p was shown to be downregulated after acute pulmonary embolism and its overexpression in vivo prevented the development of PAH in a rat model of embolism through direct targeting of both interleukin-6 (IL-6) and interleukin-1β (IL-1β) and subsequent activation of nuclear factor κβ (NF-κβ) in PASCMs [ 181 ]. miR-138-5p is upregulated in PASMCs from PAH patients as well from rats subjected to MCT-induced PAH and its inhibition restores KCNK3 and Solute carrier family 45-member 3 ( SLC45A3 ) expression and ameliorates PAH and RV function [ 182 ].…”

The Function of microRNAs in Pulmonary Embolism: Review and Research Outlook

“…In the dual-luciferase reporter assay regarding miR-340-5p, IL-1β and IL-6, both pro-inflammatory targets were confirmed to be downregulated by miR-340-5p directly, revealing a synergistic anti-inflammation effect of miR-340-5p. Therefore, miR-340-5p might be a promising therapeutic target as an anti-inflammatory agent ( Ou et al, 2020 ).…”

Overexpression of microRNA-340-5p Ameliorates Inflammatory Response and Intracellular Survival of Mycobacterium Tuberculosis in Alveolar Type II Cells

“…31 Enhanced miR-340-5p expression can inhibit the inflammatory response of pulmonary artery smooth muscle cells by declining the levels of IL-1β and IL-6. 18 It was suggested that overexpression of miR-340-5p attenuated the damage of Mtb to A549 cells by mitigating inflammatory responses and reducing Mtb survival. Subsequently, the target genes of miR-340-5p were predicted by bioinformatics website.…”

“…miR-340-5p Targets TMED7 to Mediate the NF-κB Pathway miR-340-5p can inhibit inflammation in pulmonary hypertension, neuroinflammation and heart injury by inhibiting the activation of NF-κB, [16][17][18] while TMED7 is a cisrelated gene of NF-κB. 19 Therefore, we speculated that miR-340-5p can reduce the Mtb infection-induced inflammatory responses by inhibiting TMED7 and NF-κB pathway.…”