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Review
. 2020 Nov 23;5(11):1149-1162.
doi: 10.1016/j.jacbts.2020.07.008. eCollection 2020 Nov.

Micro-RNA Analysis in Pulmonary Arterial Hypertension: Current Knowledge and Challenges

Cátia A Santos-Ferreira  1   2 , Mónica T Abreu  3   4   2 , Carla I Marques  3   4   2 , Lino M Gonçalves  1   3   4   2 , Rui Baptista  1   3   4   2   5 , Henrique M Girão  3   4   2
Affiliations
Review

Micro-RNA Analysis in Pulmonary Arterial Hypertension: Current Knowledge and Challenges

Cátia A Santos-Ferreira et al. JACC Basic Transl Sci. .

Abstract

Pulmonary arterial hypertension (PAH) is a rare, chronic disease of the pulmonary vasculature that is associated with poor outcomes. Its pathogenesis is multifactorial and includes micro-RNA (miRNA) deregulation. The understanding of the role of miRNAs in PAH is expanding quickly, and it is increasingly difficult to identify which miRNAs have the highest translational potential. This review summarizes the current knowledge of miRNA expression in PAH, discusses the challenges in miRNA analysis and interpretation, and highlights 4 promising miRNAs in this field (miR-29, miR-124, miR-140, and miR-204).

Keywords: BMPR2, bone morphogenetic protein receptor type 2; EPC, endothelial progenitor cell; HIF, hypoxia-inducible factor; HPAH, hereditary pulmonary arterial hypertension; MCT, monocrotaline; PAAF, pulmonary arterial adventitial fibroblast; PAEC, pulmonary artery endothelial cell; PAH, pulmonary arterial hypertension; PASMC, pulmonary artery smooth muscle cells; PH, pulmonary hypertension; RV, right ventricle; SU/Hx/Nx, association of Sugen 5416 with chronic hypoxia followed by normoxia; WHO, World Health Organization; animal model; lncRNA, long noncoding RNA; mRNA, messenger RNA; miRNA, micro-RNA; micro-RNA; microarray; ncRNAs, noncoding RNAs; pulmonary arterial hypertension.

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Conflict of interest statement

Dr. Baptista was supported by grants from Fundação para Ciência e Tecnologia (POCI-01-0145-FEDER-032414). Dr. Girão was supported by the European Regional Development Fund through the Operational Program for Competitiveness Factors (POCI-01-0145-FEDER-016385, CENTRO-01-0145-FEDER-000012-N2323, POCI-01-0145-FEDER-007440, CENTRO-01-0145-FEDER-032179, POCI-01-0145-FEDER-022122, UID/NEU/04539/2019, UIDB/04539/2020, and UIDP/04539/2020). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

None
Graphical abstract
Central Illustration
Central Illustration
Key Micro-RNAs Associated With Cardinal Features of Pulmonary Arterial Hypertension The miRNA dysregulation plays an important role in the hyperproliferative and apoptosis-resistant phenotype of pulmonary vascular cells in PAH, including PAECs, PASMCs, and PAAFs. This figure illustrates the lack of concordance in the pattern of expression of most miRNAs between human PAH and different animal PH models and highlights 4 miRNAs that might ultimately represent a greater potential of translating into the clinical arena. miRNA = microRNA; PAAF = pulmonary arterial adventitial fibroblasts; PAEC = pulmonary artery endothelial cell; PAH = pulmonary arterial hypertension; PASMC = pulmonary artery smooth muscle cell; PH = pulmonary hypertension; SU/Hx/Nx = association of Sugen 5416 with chronic hypoxia followed by normoxia.
Figure 1
Figure 1
Heatmap Showing logFC Expression of the miRNAs Between Patients With PAH and Healthy Control Subjects in Different Tissues The highlighted boxes represent p values <0.05. EPC = endothelial cells derived from circulating endothelial progenitor; logFC = log-fold change; miR = micro-RNA; PAH = pulmonary arterial hypertension; PASMC = pulmonary artery smooth muscle cell; PBMC = peripheral blood mononuclear cell.
Figure 2
Figure 2
Networks Representing Known Interactions Networks representing known interactions involving (A) miR-29, (B) miR-124, (C) miR-140, and (D) miR-204 related to PAH. The green arrows depict activation, whereas the red lines show inhibition. PAAF = pulmonary arterial adventitial fibroblasts; PAEC = pulmonary artery endothelial cell; other abbreviations as in Figure 1.
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