Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California; Molecular, Cellular and Integrative Physiology Graduate Program, University of California, Los Angeles, Los Angeles, California.
Division of Cardiology, Department of Internal Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California; Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, California.
Transl Res. 2019 Jul;209:121-137. doi: 10.1016/j.trsl.2019.03.001. Epub 2019 Mar 9.
Cardiovascular disease is a leading cause of mortality in the world and is exacerbated by the presence of cardiac fibrosis, defined by the accumulation of noncontractile extracellular matrix proteins. Cardiac fibrosis is directly linked to cardiac dysfunction and increased risk of arrhythmia. Despite its prevalence, there is a lack of efficacious therapies for inhibiting or reversing cardiac fibrosis, largely due to the complexity of the cell types and signaling pathways involved. Ongoing research has aimed to understand the mechanisms of cardiac fibrosis and develop new therapies for treating scar formation. Major approaches include preventing the formation of scar tissue and replacing fibrous tissue with functional cardiomyocytes. While targeting the renin-angiotensin-aldosterone system is currently used as the standard line of therapy for heart failure, there has been increased interest in inhibiting the transforming growth factor-β signaling pathway due its established role in cardiac fibrosis. Significant advances in cell transplantation therapy and biomaterials engineering have also demonstrated potential in regenerating the myocardium. Novel techniques, such as cellular direct reprogramming, and molecular targets, such as noncoding RNAs and epigenetic modifiers, are uncovering novel therapeutic options targeting fibrosis. This review provides an overview of current approaches and discuss future directions for treating cardiac fibrosis.
心血管疾病是世界上主要的死亡原因之一，其恶化的原因是心肌纤维化的存在，心肌纤维化的特征是无收缩能力的细胞外基质蛋白的积累。心肌纤维化与心脏功能障碍和心律失常风险增加直接相关。尽管其发病率很高，但目前缺乏有效抑制或逆转心肌纤维化的治疗方法，这主要是由于涉及的细胞类型和信号通路的复杂性。目前的研究旨在理解心肌纤维化的机制，并开发新的治疗瘢痕形成的方法。主要方法包括预防瘢痕组织的形成，并以功能性心肌细胞取代纤维组织。虽然靶向肾素-血管紧张素-醛固酮系统目前被用作心力衰竭的标准治疗方法，但由于转化生长因子-β信号通路在心肌纤维化中的既定作用，抑制该信号通路的兴趣有所增加。细胞移植治疗和生物材料工程的重大进展也证明了在心肌再生方面具有潜力。细胞直接重编程等新技术和非编码 RNA 和表观遗传修饰剂等分子靶点正在揭示针对纤维化的新的治疗选择。本文综述了目前的治疗方法，并讨论了治疗心肌纤维化的未来方向。
