Department of Biochemistry and Genetics, University of Navarra, 31008 Pamplona, Spain.
Program of Cardiovascular Disease, Center for Applied Medical Research (CIMA), University of Navarra, 31008 Pamplona, Spain.
Int J Mol Sci. 2024 May 30;25(11):6004. doi: 10.3390/ijms25116004.
Cardiac fibrosis, a process characterized by excessive extracellular matrix (ECM) deposition, is a common pathological consequence of many cardiovascular diseases (CVDs) normally resulting in organ failure and death. Cardiac fibroblasts (CFs) play an essential role in deleterious cardiac remodeling and dysfunction. In response to injury, quiescent CFs become activated and adopt a collagen-secreting phenotype highly contributing to cardiac fibrosis. In recent years, studies have been focused on the exploration of molecular and cellular mechanisms implicated in the activation process of CFs, which allow the development of novel therapeutic approaches for the treatment of cardiac fibrosis. Transcriptomic analyses using single-cell RNA sequencing (RNA-seq) have helped to elucidate the high cellular diversity and complex intercellular communication networks that CFs establish in the mammalian heart. Furthermore, a significant body of work supports the critical role of epigenetic regulation on the expression of genes involved in the pathogenesis of cardiac fibrosis. The study of epigenetic mechanisms, including DNA methylation, histone modification, and chromatin remodeling, has provided more insights into CF activation and fibrotic processes. Targeting epigenetic regulators, especially DNA methyltransferases (DNMT), histone acetylases (HAT), or histone deacetylases (HDAC), has emerged as a promising approach for the development of novel anti-fibrotic therapies. This review focuses on recent transcriptomic advances regarding CF diversity and molecular and epigenetic mechanisms that modulate the activation process of CFs and their possible clinical applications for the treatment of cardiac fibrosis.
心肌纤维化是一种以细胞外基质（ECM）过度沉积为特征的常见病理过程，是许多心血管疾病（CVDs）的共同病理后果，通常导致器官衰竭和死亡。心肌成纤维细胞（CFs）在有害的心肌重构和功能障碍中起着至关重要的作用。在受到损伤后，静止的 CF 会被激活并表现出分泌胶原的表型，这对心肌纤维化有很大的贡献。近年来，研究集中在探索 CF 激活过程中涉及的分子和细胞机制，这为治疗心肌纤维化提供了新的治疗方法。利用单细胞 RNA 测序（RNA-seq）的转录组分析有助于阐明 CF 在哺乳动物心脏中建立的高细胞多样性和复杂细胞间通讯网络。此外，大量的研究支持表观遗传调控对心肌纤维化发病机制相关基因表达的关键作用。对表观遗传机制的研究，包括 DNA 甲基化、组蛋白修饰和染色质重塑，为 CF 激活和纤维化过程提供了更多的见解。针对表观遗传调节剂，特别是 DNA 甲基转移酶（DNMT）、组蛋白乙酰转移酶（HAT）或组蛋白去乙酰化酶（HDAC），已成为开发新型抗纤维化治疗方法的有前途的方法。这篇综述重点介绍了最近关于 CF 多样性的转录组学进展，以及调节 CF 激活过程的分子和表观遗传机制，以及它们在治疗心肌纤维化方面的可能临床应用。
