心肌纤维化：实验模型与临床评估之间的转化差距

Myocardial Fibrosis: The Translational Gap between Experimental Models and Clinical Assessment

摘要: 心肌纤维化是心血管疾病的共同病理终点，然而相关机制的研究发现尚未充分转化为临床评估或治疗决策。本综述总结了从PubMed、Web of Science和Google Scholar检索到的有关心肌纤维化机制、实验模型、心脏磁共振、分子影像、循环生物标志物和抗纤维化治疗的研究。相关实验研究已经阐明了促纤维化信号、成纤维细胞活化、细胞外基质重塑以及疾病特异性纤维化表型，然而，常用实验模型在疾病背景、时间尺度、生物异质性和可逆性方面往往不完全等同于临床心肌纤维化。当前评估工具，尤其是心脏磁共振和循环生物标志物，主要估计结构负荷或全身性周转，但在检测活跃纤维化重塑、通路特异性和具有治疗可操作性的窗口方面仍有限。分子影像和多模态计算方法可能有助于衔接结构、功能和生物学指标检测，但需要终点层面的验证。整合生物学分层、临床相关模型选择、多模态终点验证和动态监测的闭环转化框架，可能改善抗纤维化疗法的开发，并促进对纤维化相关心血管疾病更精准的管理。

Abstract: Myocardial fibrosis is a common pathological endpoint in cardiovascular diseases; however, mechanistic insights from basic research have yet to be fully translated into clinical assessment or therapeutic decision-making. This review synthesizes current literature retrieved from PubMed, Web of Science, and Google Scholar regarding the mechanisms of myocardial fibrosis, experimental models, cardiac magnetic resonance imaging, molecular imaging, circulating biomarkers, and anti-fibrotic therapies. Preclinical studies have elucidated profibrotic signaling, fibroblast activation, extracellular matrix remodeling, and disease-specific fibrotic phenotypes. Nevertheless, commonly used experimental models often fail to fully recapitulate the clinical context of human myocardial fibrosis in terms of disease background, temporal scale, biological heterogeneity, and reversibility. Current assessment tools—particularly cardiac magnetic resonance imaging and circulating biomarkers—primarily estimate structural burden or systemic turnover but remain limited in detecting active fibrotic remodeling, pathway specificity, and actionable therapeutic windows. Molecular imaging and multimodal computational approaches hold promise for bridging structural, functional, and biological metrics, yet require validation at the endpoint level. A closed-loop translational framework integrating biological stratification, clinically relevant model selection, multimodal endpoint validation, and dynamic monitoring may enhance the development of anti-fibrotic therapies and promote precision management of fibrosis-related cardiovascular diseases.