Evaluation of Gene and microRNA Expression Patterns in Idiopathic Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension as Rare Diseases.

IF 3.1 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Respiratory medicine Pub Date : 2025-10-08 DOI:10.1016/j.rmed.2025.108415

Ecem Inci, Aybike Sena Ozuynuk-Ertugrul, Berkay Ekici, Pinar Koseoglu-Buyukkaya, Ajar Kocak, Neslihan Coban

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引用次数: 0

Abstract

Background: Pulmonary hypertension (PH) is a group of fatal diseases, including idiopathic pulmonary arterial hypertension (IPAH) and chronic thromboembolic PH (CTEPH), which are rare diseases with treatment options. Although there are suggested molecular mechanisms for IPAH, the pathogenesis of CTEPH remains unclear.

Objectives: This study hypothesized that PH-related genes and their post-transcriptional regulators, miRNAs, may show specific expression patterns in IPAH and CTEPH patients.

Methods: In this study, healthy controls (n=12), IPAH (n=15), and CTEPH (n=12) patients were recruited. The expression levels of PH-related ABCA3, ATP13A3, BMPR1A, BMPR2, KCNK3, NOTCH1, SMAD9, SOX17, and TET2 genes, along with hsa-miR-30a-5p, hsa-miR-210-3p, hsa-miR-155-5p, and hsa-miR-126-3p were determined using qRT-PCR. The associations between expression levels and clinical measurements were assessed.

Results: ABCA3 expression was decreased in IPAH (p=0.007) while SMAD9 expression was elevated in CTEPH patients (p=0.012). miR-210-3p and miR-126-3p were increased in IPAH and CTEPH, while miR-30a-5p was increased in IPAH patients (p=0.005). Moreover, systolic pulmonary artery pressure showed significant negative correlation with ATP13A3, BMPR1A, BMPR2, KCNK3, SMAD9, SOX17, and TET2 expression in IPAH patients, while NOTCH1 expression levels were positively correlated with pulmonary artery wedge pressure in CTEPH group.

Conclusions: The study identifies distinct gene and miRNA expression profiles in IPAH and CTEPH patients. Specifically, ABCA3 is downregulated in IPAH, while SMAD9 is upregulated in CTEPH, suggesting potential markers. Additionally, dysregulated miRNAs highlight the importance of post-transcriptional regulation. The correlations between gene expression and clinical parameters emphasize their prognostic value. These results represent preliminary findings and need further validation in larger cohorts.

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特发性肺动脉高压和慢性血栓栓塞性肺动脉高压罕见病的基因和microRNA表达模式评价

背景：肺动脉高压（Pulmonary hypertension， PH）是一组致死性疾病，包括特发性肺动脉高压（idiopathic Pulmonary arterial hypertension， IPAH）和慢性血栓栓塞性肺动脉高压（chronic thromboembolic PH， CTEPH），均为罕见病，有治疗选择。虽然IPAH的分子机制已被提出，但CTEPH的发病机制仍不清楚。目的：本研究假设ph相关基因及其转录后调节因子mirna可能在IPAH和CTEPH患者中表现出特定的表达模式。方法：本研究招募健康对照（n=12）、IPAH （n=15）和CTEPH （n=12）患者。采用qRT-PCR检测ph相关ABCA3、ATP13A3、BMPR1A、BMPR2、KCNK3、NOTCH1、SMAD9、SOX17、TET2基因以及hsa-miR-30a-5p、hsa-miR-210-3p、hsa-miR-155-5p、hsa-miR-126-3p基因的表达水平。评估表达水平与临床测量之间的关系。结果：IPAH患者ABCA3表达降低（p=0.007），而CTEPH患者SMAD9表达升高（p=0.012）。miR-210-3p和miR-126-3p在IPAH和CTEPH患者中升高，miR-30a-5p在IPAH患者中升高（p=0.005）。肺动脉收缩压与IPAH患者ATP13A3、BMPR1A、BMPR2、KCNK3、SMAD9、SOX17、TET2表达呈显著负相关，而NOTCH1表达水平与CTEPH组肺动脉楔压呈正相关。结论：该研究确定了IPAH和CTEPH患者中不同的基因和miRNA表达谱。具体来说，ABCA3在IPAH中下调，而SMAD9在CTEPH中上调，提示潜在的标志物。此外，失调的mirna强调了转录后调控的重要性。基因表达与临床参数之间的相关性强调了它们的预后价值。这些结果是初步发现，需要在更大的队列中进一步验证。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Respiratory medicine 医学-呼吸系统

CiteScore

7.50

自引率

0.00%

发文量

199

审稿时长

38 days

期刊介绍： Respiratory Medicine is an internationally-renowned journal devoted to the rapid publication of clinically-relevant respiratory medicine research. It combines cutting-edge original research with state-of-the-art reviews dealing with all aspects of respiratory diseases and therapeutic interventions. Topics include adult and paediatric medicine, epidemiology, immunology and cell biology, physiology, occupational disorders, and the role of allergens and pollutants. Respiratory Medicine is increasingly the journal of choice for publication of phased trial work, commenting on effectiveness, dosage and methods of action.