Ramos Mónica, Enguita Francisco Javier, Bonet Fernando, Ayala Rocío, Gómez-Pavón Francisco Javier, Campuzano Oscar, Toro Rocío, Quezada-Feijoó Maribel
Cardiology Department, Hospital Central de la Cruz Roja, 28003 Madrid, Spain.
Medicine School, Alfonso X el Sabio University, 28007 Madrid, Spain.
Biomedicines. 2025 Mar 10;13(3):671. doi: 10.3390/biomedicines13030671.
Aortic stenosis (AS) is the most common valvular pathology in the geriatric population and is the primary cause of valve replacement. However, misdiagnoses and delays in treatment are common due to comorbidities, frailty, and sedentary lifestyles among elderly individuals. MicroRNAs (miRNAs) are highly conserved molecular regulators involved in various cellular processes and have gained recognition as reliable biomarkers in cardiovascular diseases. In the present study, we evaluated plasma miRNAs as potential biomarkers for the early diagnosis of AS in the geriatric population to identify early therapeutic strategies. This prospective, case-control study included 87 individuals over 75 years of age. The participants were divided into AS (n = 58) and control (n = 29) groups. Fifty-four miRNAs were differentially expressed between patients with AS and controls. Among those genes, 29 were upregulated and 25 were downregulated in patients with AS relative to controls. We selected seven candidate genes (miR-185-5p, miR-143-3p, miR-370-3p, let-7d-3p, miR-452-5p, miR-6787-3p, and miR-21-3p) for experimental validation by qRT-PCR. Only miR-143-3p and miR-452-5p were significantly upregulated in the plasma of patients with AS compared with controls. We developed a multiparametric model by combining the two-miRNA signature with echocardiographic parameters (left ventricular ejection fraction, stroke volume, and global longitudinal strain) to increase diagnostic power; this model yielded sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) values of 78.2%, 70.7%, and 0.837, respectively. In clinical practice, the use of a multiparametric model involving this set of miRNAs combined with echocardiographic variables may improve the accuracy of AS diagnosis and risk stratification.
主动脉瓣狭窄（AS）是老年人群中最常见的瓣膜病变，也是瓣膜置换的主要原因。然而，由于老年人存在合并症、身体虚弱和久坐不动的生活方式，误诊和治疗延误很常见。微小RNA（miRNA）是参与各种细胞过程的高度保守的分子调节剂，已被公认为心血管疾病中可靠的生物标志物。在本研究中，我们评估了血浆miRNA作为老年人群AS早期诊断的潜在生物标志物，以确定早期治疗策略。这项前瞻性病例对照研究纳入了87名75岁以上的个体。参与者被分为AS组（n = 58）和对照组（n = 29）。AS患者和对照组之间有54种miRNA差异表达。在这些基因中，相对于对照组，AS患者中有29种上调，25种下调。我们选择了7个候选基因（miR-185-5p、miR-143-3p、miR-370-3p、let-7d-3p、miR-452-5p、miR-6787-3p和miR-21-3p）通过qRT-PCR进行实验验证。与对照组相比，只有miR-143-3p和miR-452-5p在AS患者血浆中显著上调。我们通过将双miRNA特征与超声心动图参数（左心室射血分数、每搏输出量和整体纵向应变）相结合，建立了一个多参数模型以提高诊断能力；该模型的敏感性、特异性和受试者工作特征曲线下面积（AUC）值分别为78.2%、70.7%和0.837。在临床实践中，使用涉及这组miRNA并结合超声心动图变量的多参数模型可能会提高AS诊断的准确性和风险分层。
