MicroRNAs in Pulmonary Hypertension, from Pathogenesis to Diagnosis and Treatment

Abstract

Pulmonary hypertension (PH) is a fatal and untreatable disease, ultimately leading to right heart failure and eventually death. microRNAs are small, non-coding endogenous RNA molecules that can regulate gene expression and influence various biological processes. Changes in microRNA expression levels contribute to various cardiovascular disorders, and microRNAs have been shown to play a critical role in PH pathogenesis. In recent years, numerous studies have explored the role of microRNAs in PH, focusing on the expression profiles of microRNAs and their signaling pathways in pulmonary artery smooth muscle cells (PASMCs) or pulmonary artery endothelial cells (PAECs), PH models, and PH patients. Moreover, certain microRNAs, such as miR-150 and miR-26a, have been identified as good candidates of diagnosis biomarkers for PH. However, there are still several challenges for microRNAs as biomarkers, including difficulty in normalization, specificity in PH, and a lack of longitudinal and big sample-sized studies. Furthermore, microRNA target drugs are potential therapeutic agents for PH treatment, which have been demonstrated in PH models and in humans. Nonetheless, synthetic microRNA mimics or antagonists are susceptible to several common defects, such as low drug efficacy, inefficient drug delivery, potential toxicity and especially, off-target effects. Therefore, finding clinically safe and effective microRNA drugs remains a great challenge, and further breakthrough is urgently needed.

CircItgb5 promotes synthetic phenotype of pulmonary artery smooth muscle cells via interacting with miR-96-5p and Uba1 in monocrotaline-induced pulmonary arterial hypertension

“…Among the candidate miRNAs, eight were previously reported to play a crucial role in PH (Fig. 5 D) [ 5 , 14 ]. In the present study, miR-96-5p was the most significantly upregulated miRNA when circItgb5 was knocked down (Fig.…”

MicroRNA in Extracellular Vesicles from Patients with Pulmonary Arterial Hypertension Alters Endothelial Angiogenic Response

“…Hierarchical clustering based on significant fold change of miR expression among PAH group divulged miscellaneous miR population ( Figure 2 C). Intriguingly, none of these miRs have been previously associated with PAH pathogenicity [ 17 ]. Gene ontology (GO) for biological processes analysis of these miRs did not result in any significant over-represented GO terms.…”

“…Additionally, some studies reported over 150 plasma-derived miRs [ 25 ] while others reported only a few [ 26 , 27 , 28 ] being dysregulated in PAH. Increasing evidence indicated more research analyzing the expression profiles of miRs and their signaling pathway in cells of the pulmonary vasculature, animal models of PAH, and PAH patients [ 17 ]. In rodent models of hypoxia-induced PAH, suppression of miR-204, miR-22, miR-30, and let-7f while up-regulation of miR-322 and miR-451 was observed [ 26 , 29 ].…”

Endothelial Function in Pulmonary Arterial Hypertension: From Bench to Bedside

“…Reintroducing miR-204 in human pulmonary ECs and mouse models has been demonstrated to enhance hemodynamic parameters and reduce the proliferation of pulmonary vascular smooth muscle cells. MiR-21 is another miRNA that is relevant to PAH; it is upregulated in rat models, as well as in the pulmonary tissues of PAH patients [94]. Through the suppression of BMPR2, a protective factor in the pathophysiology of PAH, MiR-21 encourages the proliferation and survival of smooth muscle cells in the pulmonary vascular system [95].…”