Lumish Heidi S, Sewanan Lorenzo R, Liang Lusha W, Hasegawa Kohei, Maurer Mathew S, Reilly Muredach P, Shimada Yuichi J
Division of Cardiology, Department of Medicine, Columbia University Irving Medical Center, 622 West 168 Street, PH 3 - 342, New York, NY, 10032, USA.
Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
J Cardiovasc Transl Res. 2025 Apr 14. doi: 10.1007/s12265-025-10618-x.
Hypertrophic cardiomyopathy (HCM) is the most common genetic myocardial disease, characterized by asymmetric left ventricular hypertrophy (LVH) due to sarcomeric mutations. Aortic stenosis (AS) results in concentric LVH, due to pressure overload. The aim of this study was to identify signaling pathways differentially regulated in HCM compared to AS, using plasma proteomic profiling. 76 HCM cases and 36 AS controls were matched by age and sex. A machine-learning (ML) model to predict HCM was built in the training set (70% cohort) and examined in the test set (30% cohort). Pathway analysis of proteins differentially expressed between HCM and AS was performed. The ML model accurately distinguished HCM from AS, with area under the receiver operating characteristic curve of 0.90 (95% CI: 0.79-1.00). Pathway analysis revealed differential regulation of Ras-MAPK, inflammatory and metabolic pathways. In conclusion, this study identified distinctive proteomic profiles and signaling pathways underlying LVH in HCM compared to AS.
肥厚型心肌病（HCM）是最常见的遗传性心肌病，其特征是由于肌节突变导致不对称性左心室肥厚（LVH）。主动脉瓣狭窄（AS）由于压力超负荷导致对称性LVH。本研究的目的是通过血浆蛋白质组学分析，确定与AS相比在HCM中差异调节的信号通路。76例HCM病例和36例AS对照按年龄和性别进行匹配。在训练集（70%队列）中建立了一个预测HCM的机器学习（ML）模型，并在测试集（30%队列）中进行检验。对HCM和AS之间差异表达的蛋白质进行通路分析。ML模型能准确区分HCM和AS，受试者工作特征曲线下面积为0.90（95%CI：0.79-1.00）。通路分析揭示了Ras-MAPK、炎症和代谢通路的差异调节。总之，本研究确定了与AS相比HCM中LVH潜在的独特蛋白质组学特征和信号通路。
