Fibrosis is defined by the excessive accumulation of extracellular matrix (ECM) and constitutes a central pathophysiological process that underlies tissue dysfunction, across organs, in multiple chronic diseases and during aging. Myocardial fibrosis is a key contributor to dysfunction and failure in numerous diseases of the heart and is a strong predictor of poor clinical outcome and mortality. The excess structural and matricellular ECM proteins deposited by cardiac fibroblasts, is found between cardiomyocytes (interstitial fibrosis), in focal areas where cardiomyocytes have died (replacement fibrosis), and around vessels (perivascular fibrosis). Although myocardial fibrosis has important clinical prognostic value, access to cardiac tissue biopsies for histological evaluation is limited. Despite challenges with sensitivity and specificity, cardiac magnetic resonance imaging (CMR) is the most applicable diagnostic tool in the clinic, and the scientific community is currently actively searching for blood biomarkers reflecting myocardial fibrosis, to complement the imaging techniques. The lack of mechanistic insights into specific pro- and anti-fibrotic molecular pathways has hampered the development of effective treatments to prevent or reverse myocardial fibrosis. Development and implementation of anti-fibrotic therapies is expected to improve patient outcomes and is an urgent medical need. Here, we discuss the importance of the ECM in the heart, the central role of fibrosis in heart disease, and mechanistic pathways likely to impact clinical practice with regards to diagnostics of myocardial fibrosis, risk stratification of patients, and anti-fibrotic therapy.

中文翻译：

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细胞外基质视角下的心肌纤维化：临床影响的机制


纤维化的定义是细胞外基质 （ECM） 的过度积累，构成了一个中枢病理生理过程，是跨器官、多种慢性疾病和衰老过程中组织功能障碍的基础。心肌纤维化是许多心脏疾病功能障碍和衰竭的关键因素，并且是不良临床结果和死亡率的有力预测指标。心脏成纤维细胞沉积的过量结构和基质细胞 ECM 蛋白存在于心肌细胞之间（间质纤维化）、心肌细胞死亡的局灶区域（替代纤维化）和血管周围（血管周围纤维化）。尽管心肌纤维化具有重要的临床预后价值，但用于组织学评估的心脏组织活检是有限的。尽管在灵敏度和特异性方面存在挑战，但心脏磁共振成像 （CMR） 是临床上最适用的诊断工具，科学界目前正在积极寻找反映心肌纤维化的血液生物标志物，以补充成像技术。缺乏对特定促纤维化和抗纤维化分子途径的机制见解阻碍了预防或逆转心肌纤维化的有效治疗方法的开发。抗纤维化疗法的开发和实施有望改善患者的预后，是一项紧迫的医疗需求。在这里，我们讨论了 ECM 在心脏中的重要性、纤维化在心脏病中的核心作用，以及可能影响心肌纤维化诊断、患者风险分层和抗纤维化治疗临床实践的机制途径。