Jiang Feng, Tang Jiayang, Wei Xiaoqi, Pan Hai, Fan Xinyi, Zhang Peng, Guo Shuzhen
School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing, 102488, China.
Wuhan Hospital of Traditional Chinese Medicine, Wuhan, 430014, China.
Chin Med. 2025 Jan 15;20(1):12. doi: 10.1186/s13020-025-01062-9.
Dilated cardiomyopathy (DCM) stands as one of the most prevalent and severe causes of heart failure. Inflammation plays a pivotal role throughout the progression of DCM to heart failure, while age acts as a natural predisposing factor for all cardiovascular diseases. These two factors often interact, contributing to cardiac fibrosis, which is both a common manifestation and a pathogenic driver of adverse remodeling in DCM-induced heart failure.
Bulk RNA-seq, single-cell RNA-seq, Mendelian randomization analysis, animal model construction, and BMP6 knockdown were utilized to identify and validate potential specific markers and targets for intervention in DCM heart failure.
We found that DCM hearts exhibit pronounced inflammatory cell infiltration and fibrosis. Both bulk RNA-seq and single-cell RNA-seq analyses revealed aberrant BMP6 expression specifically in fibroblasts. The ROC curve underscores the high specificity of BMP6 in relation to DCM, while Mendelian randomization analysis further confirms BMP6 as a protective factor against DCM. Notably, BMP6 knockdown led to a decrease in SMAD6 expression and a marked elevation in COL1A1 expression levels, indicating its antifibrotic role.
BMP6 emerges as a promising biomarker for DCM, and its functional role in exerting an antifibrotic effect underscores its potential as a therapeutic target.
扩张型心肌病（DCM）是心力衰竭最常见和最严重的病因之一。炎症在DCM进展为心力衰竭的整个过程中起关键作用，而年龄是所有心血管疾病的自然易感因素。这两个因素常常相互作用，导致心脏纤维化，这是DCM所致心力衰竭不良重塑的常见表现和致病驱动因素。
利用批量RNA测序、单细胞RNA测序、孟德尔随机化分析、动物模型构建和BMP6基因敲低来识别和验证DCM心力衰竭潜在的特异性标志物和干预靶点。
我们发现DCM心脏表现出明显的炎症细胞浸润和纤维化。批量RNA测序和单细胞RNA测序分析均显示BMP6在成纤维细胞中表达异常。ROC曲线强调了BMP6与DCM相关的高特异性，而孟德尔随机化分析进一步证实BMP6是预防DCM的保护因子。值得注意的是，BMP6基因敲低导致SMAD6表达降低，COL1A1表达水平显著升高，表明其抗纤维化作用。
BMP6是一种有前景的DCM生物标志物，其发挥抗纤维化作用的功能特性突出了其作为治疗靶点的潜力。
