Cenerini Giovanni, Chimera Davide, Pagnini Marta, Bazzan Erica, Conti Maria, Turato Graziella, Celi Alessandro, Neri Tommaso
UO Pneumologia, Azienda Ospedaliero-Universitaria Pisana, 56124 Pisa, Italy.
Centro Dipartimentale di Biologia Cellulare Cardiorespiratoria, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Università degli Studi di Pisa, 56124 Pisa, Italy.
Cells. 2024 Dec 18;13(24):2099. doi: 10.3390/cells13242099.
Idiopathic pulmonary fibrosis (IPF) is associated with a significantly increased risk of thrombotic events and mortality. This review explores the complex bidirectional relationship between pulmonary fibrosis and thrombosis, discussing epidemiological evidence, pathogenetic mechanisms, and therapeutic implications, with a particular focus on the emerging role of extracellular vesicles (EVs) as crucial mediators linking fibrosis and coagulation. Coagulation factors directly promote fibrosis, while fibrosis itself activates thrombotic pathways. Retrospective studies suggest the benefits of anticoagulants in IPF, but prospective trials have faced challenges. Novel anticoagulants, profibrinolytic therapies, and agents targeting protease-activated receptors (PARs) show promise in preclinical studies and early clinical trials. EVs have emerged as key players in the pathogenesis of interstitial lung diseases (ILDs), serving as vehicles for intercellular communication and contributing to both fibrosis and coagulation. EV-based approaches, such as EV modulation, engineered EVs as drug delivery vehicles, and mesenchymal stem cell-derived EVs, represent promising therapeutic strategies. Ongoing research should focus on optimizing risk-benefit profiles, identifying predictive biomarkers, evaluating combination strategies targeting thrombotic, fibrotic, and inflammatory pathways, and advancing the understanding of EVs in ILDs to develop targeted interventions.
特发性肺纤维化（IPF）与血栓形成事件及死亡率的显著增加相关。本综述探讨了肺纤维化与血栓形成之间复杂的双向关系，讨论了流行病学证据、发病机制及治疗意义，特别关注细胞外囊泡（EVs）作为连接纤维化和凝血的关键介质的新作用。凝血因子直接促进纤维化，而纤维化本身激活血栓形成途径。回顾性研究提示抗凝剂对IPF有益，但前瞻性试验面临挑战。新型抗凝剂、促纤溶疗法及靶向蛋白酶激活受体（PARs）的药物在临床前研究和早期临床试验中显示出前景。EVs已成为间质性肺疾病（ILDs）发病机制中的关键因素，作为细胞间通讯的载体，对纤维化和凝血均有作用。基于EVs的方法，如EVs调节、将工程化EVs作为药物递送载体以及间充质干细胞衍生的EVs，代表了有前景的治疗策略。正在进行的研究应聚焦于优化风险效益比、识别预测性生物标志物、评估针对血栓形成、纤维化和炎症途径的联合策略，以及加深对ILDs中EVs的理解以开发靶向干预措施。
