MicroRNA and lncRNA as the Future of Pulmonary Arterial Hypertension Treatment

Abstract

Pulmonary hypertension (PH) is characterized by a progressive increase in pulmonary arterial pressure and pulmonary vascular resistance. In a short time, it leads to right ventricular failure and, consequently, to death. The most common causes of PH include left heart disease and lung disease. Despite the significant development of medicine and related sciences observed in recent years, we still suffer from a lack of effective treatment that would significantly influence the prognosis and prolong life expectancy of patients with PH. One type of PH is pulmonary arterial hypertension (PAH). The pathophysiology of PAH is based on increased cell proliferation and resistance to apoptosis in the small pulmonary arteries, leading to pulmonary vascular remodeling. However, studies conducted in recent years have shown that epigenetic changes may also lie behind the pathogenesis of PAH. Epigenetics is the study of changes in gene expression that are not related to changes in the sequence of nucleotides in DNA. In addition to DNA methylation or histone modification, epigenetic research focuses on non-coding RNAs, which include microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). Preliminary research results give hope that targeting epigenetic regulators may lead to new, potential therapeutic possibilities in the treatment of PAH.

An endothelial regulatory module links blood pressure regulation with elite athletic performance

“…Imminent evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in pulmonary vascular remodeling and pulmonary arterial hypertension (PAH) [ 70 ]. LncRNAs are implicated in regulating chromatin structure, thereby leading to pulmonary arterial endothelial dysfunction by modulating endothelial cell proliferation, angiogenesis, endothelial mesenchymal transition, and metabolism [ 71 ]. Targeting epigenetic regulators may lead to new, potential therapeutic possibilities in treating PAH [ 71 ].…”

“…LncRNAs are implicated in regulating chromatin structure, thereby leading to pulmonary arterial endothelial dysfunction by modulating endothelial cell proliferation, angiogenesis, endothelial mesenchymal transition, and metabolism [ 71 ]. Targeting epigenetic regulators may lead to new, potential therapeutic possibilities in treating PAH [ 71 ]. It is clear that the search for potential lncRNAs regulating this wider genomic region in horses are required, but even so, these four directly interactive genes comprise promising candidates that warrant further investigation.…”

Roles of LncRNAs in the Pathogenesis of Pulmonary Hypertension

“…Mechanistically, MEG3 was found to interact with and lead to the degradation of miRNA-328-3p, contributing to the upregulation of insulin-like growth factor 1 receptor (IGF1R), which promotes PASMC proliferation and cell cycle progression [31]. Notably, in a 2019 study by Xing et al [31] revealing the pathogenic relevance of the lncRNA MEG3 in PH, with completely opposite results to a 2017 study [66]. To explain these inconsistent results, Xing et al [31] proposed numerous hypotheses: First, the reason may be related to the different selections of the 15 MEG3 transcript variants.…”

Epigenetics of hypertension as a risk factor for the development of coronary artery disease in type 2 diabetes mellitus

“…Importantly, this treatment resulted in a significant reduction in the activation of the STAT3–NFAT signaling pathway, leading to reduced proliferation and increased susceptibility to apoptosis in pulmonary arterial smooth muscle cells (PASMCs). Additionally, the downregulation of miR-204 in the buffy coat suggests its potential utility as a diagnostic marker for PAH ( 114 ).…”