MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1

Baptista, Rui; Marques, Célio Gonçalo; Catarino, Steve; Enguita, Francisco J.; Costa, Marina C.; Matafome, Paulo; Zuzarte, Mónica; Castro, Graça; Reis, Abílio; Monteiro, Pedro; Pêgo, M.; Pereira, Paulo; Girão, Henrique

doi:10.1093/cvr/cvx187

Cited by 79 publications

(69 citation statements)

References 44 publications

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“…Such an explanation gains some support from a recent study investigating circulating levels of miR‐322‐5p in response to MCT . This study showed that miR‐322‐5p in circulation is elevated 1 week after treatment and then decreases at 2 weeks only to increase again by 6 weeks.…”

Section: Discussionmentioning

confidence: 83%

miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

et al. 2018

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Pulmonary arterial hypertension ( PAH ) is characterised by remodelling of the pulmonary vasculature leading to right ventricular hypertrophy. Here, we show that miR‐322‐5p (the rodent orthologue of miR‐424‐5p) expression is decreased in the right ventricle of monocrotaline‐treated rats, a model of PAH , whereas a putative target insulin‐like growth factor 1 ( IGF ‐1) is increased. IGF ‐1 mRNA was enriched 16‐fold in RNA immunoprecipitated with Ago2, indicating binding to miR‐322‐5p. In cell transfection experiments, miR‐322‐5p suppressed the activity of a luciferase reporter containing a section of the IGF ‐1 3′ untranslated region ( UTR ) as well as IGF ‐1 mRNA and protein levels. Taken together, these data suggest that miR‐322 targets IGF ‐1, a process downregulated in PAH ‐related RV hypertrophy.

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Section: Discussionmentioning

confidence: 83%

miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

et al. 2018

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“…Luckily, a recent study showed that plasma miR-424(322) is significantly up-regulated in the global cohort of pulmonary hypertension (PH) patients and in the subgroup of PAH patients and correlates with the prognosis and severity of disease, and higher levels of miR-424(322) are predictive of event-free survival. 183 Therefore, plasma miR-424(322) is considered to be a unique value biomarker for the diagnosis and prognostic of PH patients. In addition, miR-19a expression is significantly elevated in plasma and in PAH lung tissues, 184 whereas miR-124 expression is down-regulated in blood outgrowth endothelial cells (BOECs) from PAH patients.…”

Section: Pulmonary Arterial Hypertensionmentioning

confidence: 99%

The regulatory role of microRNAs in angiogenesis‐related diseases

Sun

Lei

et al. 2018

J Cellular Molecular Medi

119

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MicroRNAs (miRNAs) are small non‐coding RNAs that regulate gene expression at a post‐transcriptional level via either the degradation or translational repression of a target mRNA. They play an irreplaceable role in angiogenesis by regulating the proliferation, differentiation, apoptosis, migration and tube formation of angiogenesis‐related cells, which are indispensable for multitudinous physiological and pathological processes, especially for the occurrence and development of vascular diseases. Imbalance between the regulation of miRNAs and angiogenesis may cause many diseases such as cancer, cardiovascular disease, aneurysm, Kawasaki disease, aortic dissection, phlebothrombosis and diabetic microvascular complication. Therefore, it is important to explore the essential role of miRNAs in angiogenesis, which might help to uncover new and effective therapeutic strategies for vascular diseases. This review focuses on the interactions between miRNAs and angiogenesis, and miRNA‐based biomarkers in the diagnosis, treatment and prognosis of angiogenesis‐related diseases, providing an update on the understanding of the clinical value of miRNAs in targeting angiogenesis.

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“…The overall importance of miRNAs in the cardiovascular system was established, such as PAH. Studies revealed that the expression level of miRNAs in human lungs with PAH is changed (Baptista et al, ). Several research tried to explore the effect of miRNAs on the phenotypic change due to enhanced proliferation of pulmonary artery smooth muscle cells (PASMCs) in PAH.…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

MicroRNA‐140‐5p targeting tumor necrosis factor‐α prevents pulmonary arterial hypertension

Zhu

Zhang

Yin

et al. 2018

Journal Cellular Physiology

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Background Pulmonary arterial hypertension (PAH) is characterized by the apoptosis resistance and hyperproliferation of pulmonary artery smooth muscle cells (PASMCs). Its pathogenesis has not been revealed. Here, we carried out experiments to investigate the functions of miR‐140‐5p and tumor necrosis factor‐α (TNF‐α). Methods We selected GSE703 from Gene Expression Omnibus (GEO) Database to conduct microarray analysis using R software and Gene Set Enrichment Analysis (GSEA). Combing bioinformatics results, the upregulation of miR‐140‐5p inhibited PAH progression through targeting TNF‐α. RNA expression was measured by quantitative real‐time polymerase chain reaction (RT‐qPCR) and protein level was measured by western blot analysis and enzyme‐linked immunosorbent assays (ELISA). We conducted monocrotaline (MCT) injection to rats to form PAH animal models. The lung tissues were observed by hematoxylin–eosin (HE) staining and Sirius red‐picric acid staining. Right ventricular systolic pressure (RVSP) and the ratio of right ventricle (RV)‐to‐left ventricle (LV) plus septum (S) weight (RV/[LV + S]) were measured in MCT‐induced animal models. Overexpression of miR‐140‐5p and TNF‐α were utilized to research the proliferation, migration, and phenotypic variation of hypoxia‐mediated PASMCs. The binding between miR‐140‐5p and TNF‐α 3′‐untranslated region (3′‐UTR) was confirmed via luciferase reporter assay. Results Downregulation of miR‐140‐5p and upregulation of TNF‐α were observed in PAH rat model and hypoxia‐mediated PASMCs. And we proved that overexpression of miR‐140‐5p could suppress the proliferation, migration, and phenotypic variation of PASMCs, therefore inhibiting PAH pathogenesis. Luciferase assay verified that miR‐140‐5p targeted TNF‐α directly. A converse correlation was also shown between miR‐140‐5p and TNF‐α in PASMCs. Conclusions miR‐140‐5p and TNF‐α are important regulators in PAH pathology and may serve as a therapeutic target for PAH.

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MicroRNA-424(322) as a new marker of disease progression in pulmonary arterial hypertension and its role in right ventricular hypertrophy by targeting SMURF1

Cited by 79 publications

References 44 publications

miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

miR‐322‐5p targets IGF‐1 and is suppressed in the heart of rats with pulmonary hypertension

The regulatory role of microRNAs in angiogenesis‐related diseases

MicroRNA‐140‐5p targeting tumor necrosis factor‐α prevents pulmonary arterial hypertension

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