Cai Huiling, Yu Cheng, Li Xiuchuan, Wang Xuenan, Yang Yongjian, Lan Cong
Department of Cardiology, School of Clinical Medicine, Southwest Medical University, Luzhou, Sichuan, China.
Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, Sichuan, China.
Front Cardiovasc Med. 2025 Jan 29;12:1518022. doi: 10.3389/fcvm.2025.1518022. eCollection 2025.
Clinical practice currently faces a significant shortfall in specific biomarkers needed for diagnosing right ventricular (RV) remodeling in patients with pulmonary hypertension (PH). While small noncoding microRNAs (miRNAs) are crucial regulators of RV remodeling, the biomarker potential of serum miRNAs in this process is little known. This study systematically screened and identified candidate serum miRNAs as potential diagnostic biomarkers for RV remodeling in PH patients.
Pulmonary artery banding (PAB) was performed in Sprague-Dawley (SD) rats and RV modeling was measured by echocardiographic and histological analyses 4 weeks after surgery. High-throughput miRNA sequencing of serum samples was performed to profile differentially-expressed miRNAs (dif-miRNAs) and preliminarily screen candidate miRNAs. The diagnostic power of the candidate miRNA was further validated in 100 patients [20 with adaptive RV pressure overload; 20 with maladaptive RV pressure overload; 20 with left heart failure (LHF); 19 with left ventricular hypertrophy and 21 controls].
PAB rats exhibited severe RV hypertrophy, fibrosis and enlargement of RV cardiomyocytes compared with sham group. MiRNA sequencing analyses revealed 19 dif-miRNAs (12 upregulated and 7 downregulated) between the two groups. Among the 12 upregulated miRNAs, miRNA-486 exhibited highest elevation in PAB group and was supposed to be the candidate biomarker for RV modeling. Serum miRNA-486 levels were lower in control and left ventricular hypertrophy (LVH) patients compared to PH patients, and significantly higher in maladapted RV patients than in adapted RV patients. Serum miRNA-486 was significantly higher in LHF patients compared to controls, but still significantly lower than in PH patients. In receiver operating characteristic (ROC) analysis, serum miRNA-486 was a good predictor of RV maladaptation in PH patients (cut-off value 3.441, AUC 0.8625), which was not significantly different from B-type natriuretic peptide (BNP). Elevated serum miRNA-486 levels (≥3.441) were associated with reduced TAPSE/PASP ratios and increased BNP levels.
Serum miRNA-486 has the potential to be a valuable noninvasive biomarker for diagnosing RV remodeling in patients with PH.
临床实践目前在诊断肺动脉高压（PH）患者右心室（RV）重塑所需的特定生物标志物方面存在重大短缺。虽然小的非编码微小RNA（miRNA）是RV重塑的关键调节因子，但血清miRNA在此过程中的生物标志物潜力鲜为人知。本研究系统地筛选并鉴定了候选血清miRNA作为PH患者RV重塑的潜在诊断生物标志物。
对Sprague-Dawley（SD）大鼠进行肺动脉环扎（PAB），术后4周通过超声心动图和组织学分析测量RV建模。对血清样本进行高通量miRNA测序，以分析差异表达的miRNA（dif-miRNA）并初步筛选候选miRNA。在100例患者中进一步验证候选miRNA的诊断能力[20例适应性RV压力过载；20例适应性不良的RV压力过载；20例左心衰竭（LHF）；19例左心室肥厚和21例对照]。
与假手术组相比，PAB大鼠表现出严重的RV肥厚、纤维化和RV心肌细胞增大。miRNA测序分析显示两组之间有19种dif-miRNA（12种上调和7种下调）。在12种上调的miRNA中，miRNA-486在PAB组中升高最高，被认为是RV建模的候选生物标志物。与PH患者相比，对照组和左心室肥厚（LVH）患者的血清miRNA-486水平较低，适应性不良的RV患者明显高于适应性RV患者。与对照组相比，LHF患者的血清miRNA-486明显更高，但仍明显低于PH患者。在受试者工作特征（ROC）分析中，血清miRNA-486是PH患者RV适应性不良的良好预测指标（临界值3.441，AUC 0.8625），与B型利钠肽（BNP）无显著差异。血清miRNA-486水平升高（≥3.441）与TAPSE/PASP比值降低和BNP水平升高有关。
血清miRNA-486有可能成为诊断PH患者RV重塑的有价值的非侵入性生物标志物。
