Cabrera-Fuentes Hector A, Barreto Guillermo, Perez-Campos Eduardo, Nivon-Torres Gilka F, Garcia González Aldo Abel, Al-Suhaim Ebtesam Abdullah, Liehn Elisa A
División de Estudios de Posgrado e Investigación, Tecnológico Nacional de México/Instituto Tecnológico de Tijuana, Tijuana, México.
R&D Group, Vice Presidency Scientific Research & Innovation, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia.
FASEB J. 2025 Sep 15;39(17):e71008. doi: 10.1096/fj.202500970R.
Cardiovascular diseases are increasingly recognized as chronic disorders driven by a complex interplay between inflammation and fibrosis. In this review, we elucidate emerging mechanisms that govern the transition from acute inflammation to pathological fibrosis, with particular focus on cellular crosstalk between neutrophils, macrophages, fibroblasts, and myofibroblasts. We explore how dysregulated immune responses and extracellular matrix (ECM) remodeling sustain a pathogenic feedback loop, promoting myocardial stiffening and adverse cardiac remodeling. Special attention is given to the plasticity of immune and stromal cells, including macrophage polarization and fibroblast-to-myofibroblast transitions, as well as the roles of TGF-β signaling, hypoxia, and noncoding RNAs. Building on this mechanistic foundation, we highlight next-generation therapeutic strategies-ranging from immunometabolic and epigenetic reprogramming to gene editing, cell-based therapies, and nanomedicine-designed to interrupt the inflammation-fibrosis axis. By targeting these interconnected pathways, emerging therapies offer the potential to reverse maladaptive remodeling, restore cardiac function, and redefine the treatment landscape in cardiovascular disease.
心血管疾病越来越被认为是由炎症和纤维化之间复杂的相互作用驱动的慢性疾病。在这篇综述中，我们阐明了控制从急性炎症向病理性纤维化转变的新机制，特别关注中性粒细胞、巨噬细胞、成纤维细胞和肌成纤维细胞之间的细胞间相互作用。我们探讨了失调的免疫反应和细胞外基质（ECM）重塑如何维持致病反馈回路，促进心肌僵硬和不良心脏重塑。特别关注免疫和基质细胞的可塑性，包括巨噬细胞极化和成纤维细胞向肌成纤维细胞的转变，以及转化生长因子-β（TGF-β）信号传导、缺氧和非编码RNA的作用。基于这一机制基础，我们强调了下一代治疗策略，从免疫代谢和表观遗传重编程到基因编辑、细胞疗法和纳米医学，旨在中断炎症-纤维化轴。通过靶向这些相互关联的途径，新兴疗法有可能逆转适应性不良的重塑，恢复心脏功能，并重新定义心血管疾病的治疗格局。
