Fan Dong, Feng Han, Song Mengyu, Tan Penglin
Department of Pathophysiology, Zhuhai Campus of Zunyi Medical University, Zhuhai, 519041, China.
National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Mol Cell Biochem. 2025 Mar;480(3):1555-1567. doi: 10.1007/s11010-024-05126-6. Epub 2024 Oct 5.
Hypertensive and ischemic heart diseases have high morbidity all over the world, and they primarily contribute to heart failure associated with high mortality. Cardiac remodeling, as a basic pathological process in heart diseases, is mainly comprised of cardiac hypertrophy and fibrosis, as well as cell death which occurs especially in the ischemic cardiomyopathy. Myocardial remodeling has been widely investigated by a variety of animal models, including pressure overload, angiotensin II stimulation, and myocardial infarction. Pressure overload can cause compensatory cardiac hypertrophy at the early stage, followed by decompensatory hypertrophy and heart failure at the end. Recently, RNA sequencing and differentially expressed gene (DEG) analyses have been extensively employed to elucidate the molecular mechanisms of cardiac remodeling and related heart failure, which also provide potential targets for high-throughput drug screenings. In this review, we summarize recent advancements in gene expression profiling, related gene functions, and signaling pathways pertinent to myocardial remodeling induced by pressure overload at distinct stages, ischemia-reperfusion, myocardial infarction, and diabetes. We also discuss the effects of sex differences and inflammation on DEGs and their transcriptional regulatory mechanisms in cardiac remodeling. Additionally, we summarize emerging therapeutic agents and strategies aimed at modulating gene expression profiles during myocardial remodeling.
高血压性心脏病和缺血性心脏病在全球范围内发病率很高，它们是导致心力衰竭且死亡率高的主要原因。心脏重塑作为心脏病的一个基本病理过程，主要包括心肌肥大、纤维化以及细胞死亡，后者尤其发生在缺血性心肌病中。人们已经通过多种动物模型对心肌重塑进行了广泛研究，包括压力超负荷、血管紧张素II刺激和心肌梗死。压力超负荷在早期可导致代偿性心肌肥大，最终发展为失代偿性肥大和心力衰竭。最近，RNA测序和差异表达基因（DEG）分析已被广泛用于阐明心脏重塑及相关心力衰竭的分子机制，这也为高通量药物筛选提供了潜在靶点。在这篇综述中，我们总结了在基因表达谱、相关基因功能以及与压力超负荷、缺血再灌注、心肌梗死和糖尿病在不同阶段诱导的心肌重塑相关的信号通路方面的最新进展。我们还讨论了性别差异和炎症对心脏重塑中差异表达基因及其转录调控机制的影响。此外，我们总结了旨在调节心肌重塑过程中基因表达谱的新兴治疗药物和策略。
