Pulmonary Arterial Hypertension and MicroRNAs—An Ever-growing Partnership

Wang, Yong; Xue, Xinying; Liu, Yuxia; Wang, Kai‐Fei; Zang, Xuefeng; Wang, Jing; Wang, Pei-lan; Zhang, Jie; Pan, Lei; Zhang, Shuyang; Wang, Jianxin

doi:10.1016/j.arcmed.2013.08.003

Cited by 11 publications

(8 citation statements)

References 31 publications

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“…Other events, including abnormal proliferation of endothelial cells, inflammation, thrombosis and platelet dysfunction are also common (1,4,20). Given the universal role of miRNA in biological regulation, it is expected that certain miRNAs, including miR-32, 20, 245 and 122 have been reported to be involved in PAH (21). The present study identified certain novel miRNAs by employing a comprehensive miRNA array screening, including miR-125-3p, miR-148-3p and miR-193.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of microRNA in the lungs of rats with pulmonary arterial hypertension

Xiao

Xie

Huang

et al. 2016

Molecular Medicine Reports

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Pulmonary arterial hypertension (PAH) is a chronic disorder of the small pulmonary arteries, and the efficacy of the therapies and the prognosis remain poor. The pathobiology of PAH is complex, and needs to be elucidated by multiple approaches. The present study used a monocrotaline-induced PAH rat model to perform a comprehensive microRNA (miRNA) microarray screening in the lungs and identified 16 downregulated miRNAs in the lungs from PAH rats. High-enrichment gene ontology (GO) analysis identified several sets of genes, and established the miRNA-mRNA network by outlining the interactions of miRNA and GO-associated genes. Three downregulated miRNAs [miRNA 125-3p (miR-125-3p), miR-148-3p and miR-193] displayed the most marked regulatory function, and miR-148-3p and miR-193 were observed to have the highest number of target mRNAs. Signaling pathway analysis demonstrated 26 signal transduction pathways, with MAPK, TGF-β and cell cycle signaling as the most prominent. In addition, 342 genes were identified as the potential targets of these 16 miRNAs. Thus, a set of miRNAs in the lungs from rats with PAH and novel associations between biological events and PAH pathogenesis were identified, providing potential therapeutic targets for this disorder.

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Section: Discussionmentioning

confidence: 99%

Differential expression of microRNA in the lungs of rats with pulmonary arterial hypertension

Xiao

Xie

Huang

et al. 2016

Molecular Medicine Reports

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“…Pulmonary arterial hypertension is a debilitating condition with progressive remodeling of the pulmonary resistance vessels [ 22 ]. It is characterized by excessive vascular resistance and smooth muscle cell proliferation in small pulmonary arteries and finally causes elevation of pulmonary vascular resistance, right ventricular failure, and death [ 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Unfortunately, because of the lack of a specific method of detecting RHD, many patients have been diagnosed with irreversible valvular dysfunction, for which valvular surgery is one of the main treatments. RHD continues to be a burden in several developing countries such as India and China, though it is reasonably rare in western countries—probably because of the widespread use of antibiotics [ 20 – 22 ]. Therefore, the identification of a biomarker of characteristic RHD pathophysiology will be valuable to aid early detection and enable patients to avoid surgery by starting effective treatment at an early stage.…”

Section: Introductionmentioning

confidence: 99%

“…Pulmonary arterial hypertension (PAH) is a common complication of many RHD patients. Because PAH is characterized by the enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells [ 23 ], and as some miRNAs are also associated with the regulation of cell proliferation and apoptosis, it is hypothesized that they might be implicated in the etiology of PAH [ 22 – 26 ].…”

Section: Introductionmentioning

confidence: 99%

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Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR-1183 and miR-1299 as Potential Diagnostic Biomarkers

Lian

Zhao

et al. 2015

BioMed Research International

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This study compared microRNA (miRNA) expression profiles between rheumatic heart disease (RHD) patients and healthy controls to investigate their differential expression and help elucidate their mechanisms of action. Microarray analysis was used to measure miRNA expression, and a total of 133 miRNAs were shown to be significantly upregulated in RHD patients compared with controls, including miR-1183 and miR-1299. A total of 137 miRNAs, including miR-4423-3p and miR-218-1-3p, were significantly downregulated in RHD patients. Quantitative real-time-PCR confirmed microarray findings for miR-1183 and miR-1299 in both tissue and plasma. Bioinformatic predictions were also made of differentially expressed miRNAs as biomarkers in RHD by databases and GO/pathway analysis. Furthermore, we investigated miR-1183 and miR-1299 expression in RHD patients with secondary pulmonary hypertension (PAH). Our findings identified an important role for miR-1299 as a direct regulator of RHD, while the observed difference in expression of miR-1183 between RHD-PAH patients with high or low pulmonary artery pressure suggests that miR-1183 overexpression may reflect pulmonary artery remodeling. miR-1183 and miR-1299 appear to play distinct roles in RHD pathogenesis accompanied by secondary PAH and could be used as potential biological markers for disease development.

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“…There is no cure of this disease and current therapies are limited to reverse the vascular remodeling. Evolving evidence indicates that dysregulation of microRNAs (miRNA or miR) contributes to PH pathogenesis [ 19 – 24 ]. Indeed, an emerging body of evidence demonstrates that a fine balance in miRNA levels seems to be a fundamental to maintaining homeostasis in the pulmonary vasculature and an imbalance with miRNA level playing a critical role in the pathogenesis of PH by regulating a set of targeted genes [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Modulation of miRNAs in Pulmonary Hypertension

Gupta¹,

2015

International Journal of Hypertension

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MicroRNAs (miRNAs) have emerged as a new class of posttranscriptional regulators of many cardiac and vascular diseases. They are a class of small, noncoding RNAs that contributes crucial roles typically through binding of the 3′-untranslated region of mRNA. A single miRNA may influence several signaling pathways associated with cardiac remodeling by targeting multiple genes. Pulmonary hypertension (PH) is a rare disorder characterized by progressive obliteration of pulmonary (micro) vasculature that results in elevated vascular resistance, leading to right ventricular hypertrophy (RVH) and RV failure. The pathology of PH involves vascular cell remodeling including pulmonary arterial endothelial cell (PAEC) dysfunction and pulmonary arterial smooth muscle cell (PASMC) proliferation. There is no cure for this disease. Thus, novel intervention pathways that govern PH induced RVH may result in new treatment modalities. Current therapies are limited to reverse the vascular remodeling. Recent studies have demonstrated the roles of various miRNAs in the pathogenesis of PH and pulmonary disorders. This review provides an overview of recent discoveries on the role of miRNAs in the pathogenesis of PH and discusses the potential for miRNAs as therapeutic targets and biomarkers of PH at clinical setting.

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Pulmonary Arterial Hypertension and MicroRNAs—An Ever-growing Partnership

Cited by 11 publications

References 31 publications

Differential expression of microRNA in the lungs of rats with pulmonary arterial hypertension

Differential expression of microRNA in the lungs of rats with pulmonary arterial hypertension

Detection of Differentially Expressed MicroRNAs in Rheumatic Heart Disease: miR-1183 and miR-1299 as Potential Diagnostic Biomarkers

Modulation of miRNAs in Pulmonary Hypertension

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