表型
串扰
心脏纤维化
下调和上调
纤维化
肌成纤维细胞
压力过载
内皮功能障碍
细胞生物学
内皮干细胞
生物
肌肉肥大
医学
癌症研究
病理
内科学
内分泌学
物理
遗传学
基因
心力衰竭
光学
心肌肥大
体外
作者
Yue Li,Shi-Hao Ni,Xin Liu,Shu-Ning Sun,Gui-Chen Ling,Jianping Deng,Xiao-Lu Ou-Yang,Yu‐Sheng Huang,Huan Li,Zixin Chen,Xiufang Huang,Shaoxiang Xian,Zhong‐Qi Yang,Lingjun Wang,Wu Hongyan,Lu Lu
标识
DOI:10.1016/j.ejphar.2024.176378
摘要
Heart failure (HF) is a complex chronic condition characterized by structural and functional impairments. The differentiation of endothelial cells into myofibroblasts (EndoMT) in response to cardiac fibrosis is controversial, and the relative contribution of endothelial plasticity remains to be explored. Single-cell RNA sequencing was used to identify endothelial cells undergoing fibrotic differentiation within 2 weeks of transverse aortic constriction (TAC). This subset of endothelial cells transiently expressed fibrotic genes but had low expression of alpha-smooth muscle actin, indicating a non-canonical EndoMT, which we named a transient fibrotic-like phenotype (EndoFP). The role of EndoFP in pathological cardiac remodeling may be correlated with increased levels of osteopontin. Cardiomyocytes and fibroblasts co-cultured with EndoFP exhibited heightened pro-hypertrophic and pro-fibrotic effects. Mechanistically, we found that the upregulated expression of insulin-like growth factor-binding protein 5 may be a key mediator of EndoFP-induced cardiac dysfunction. Furthermore, our findings suggested that Rab5a is a novel regulatory gene involved in the EndoFP process. Our study suggests that the specific endothelial subset identified in TAC-induced pressure overload plays a critical role in the cellular interactions that lead to cardiac fibrosis and hypertrophy. Additionally, our findings provide insight into the mechanisms underlying EndoFP, making it a potential therapeutic target for early heart failure.
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