Role of Long Non-Coding RNAs in Pulmonary Arterial Hypertension

Abstract

Pulmonary arterial hypertension (PAH) is a debilitating condition of the pulmonary circulatory system that occurs in patients of all ages and if untreated, eventually leads to right heart failure and death. Despite existing medical treatment options that improve survival and quality of life, the disease remains incurable. Thus, there is an urgent need to develop novel therapies to treat this disease. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in pulmonary vascular remodeling and PAH. LncRNAs are implicated in pulmonary arterial endothelial dysfunction by modulating endothelial cell proliferation, angiogenesis, endothelial mesenchymal transition, and metabolism. LncRNAs are also involved in inducing different pulmonary arterial vascular smooth muscle cell phenotypes, such as cell proliferation, apoptosis, migration, regulation of the phenotypic switching, and cell cycle. LncRNAs are essential regulators of gene expression that affect various diseases at the chromatin, transcriptional, post-translational, and even post-translational levels. Here, we focus on the role of LncRNAs and their molecular mechanisms in the pathogenesis of PAH. We also discuss the current research challenge and potential biomarker and therapeutic potentials of lncRNAs in PAH.

Epigenetic Mechanisms as Emerging Therapeutic Targets and Microfluidic Chips Application in Pulmonary Arterial Hypertension

“…They are mainly located in the nucleus of the cell, along with a low level of expression. They play an important epigenetic role by functioning as suppressors or activators of gene transcription and mRNA translation, miRNA precursors, RNA stabilizers, and sponges [ 165 ]. Emerging evidence has demonstrated a link between lncRNAs and the initiation of various human diseases, including cancer and cardiovascular and neurodegenerative diseases [ 165 ].…”

“…They play an important epigenetic role by functioning as suppressors or activators of gene transcription and mRNA translation, miRNA precursors, RNA stabilizers, and sponges [ 165 ]. Emerging evidence has demonstrated a link between lncRNAs and the initiation of various human diseases, including cancer and cardiovascular and neurodegenerative diseases [ 165 ]. Pathological changes of PAH include excessive cell proliferation, migration, and a loss of balance between cell growth and death induced by apoptosis.…”

“…Although many lncRNAs have been detected in PAH patient samples and preclinical animal models [ 165 ], there are no clinical trials targeting lncRNAs in PAH that have been developed. There are several reasons, including poor conservation across the species, the stability of lncRNAs in blood circulation, the lack of proper drug delivery systems, routes, and doses, and nonspecific toxicities.…”

Long Noncoding RNAs: Emerging Regulators of Platelet-derived Growth Factor Signaling

“…Several studies have shown that lncRNAs such as H19, TYKRIL, MEG3, MANTIS and HOXA-AS3 play major role in PH development and progression [5].…”

“…Considering the pivotal role of lncRNAs in regulating various biological processes, lncRNA-based therapies represent a promising therapeutic approach, especially for diseases with poor treatment options, such as PH. Several studies have shown that lncRNAs, such as H19, TYKRIL, MEG3, MANTIS, and HOXA-AS3, play a major role in PH development and progression ( 5 ).…”