Medizinische Klinik und Poliklinik I, University Hospital, LMU Munich, Munich, Germany.
German Center for Cardiovascular Research (DZHK), partner site Munich Heart Alliance, Munich, Germany.
Nat Rev Cardiol. 2021 Sep;18(9):666-682. doi: 10.1038/s41569-021-00552-1. Epub 2021 May 6.
Thrombosis is the most feared complication of cardiovascular diseases and a main cause of death worldwide, making it a major health-care challenge. Platelets and the coagulation cascade are effectively targeted by antithrombotic approaches, which carry an inherent risk of bleeding. Moreover, antithrombotics cannot completely prevent thrombotic events, implicating a therapeutic gap due to a third, not yet adequately addressed mechanism, namely inflammation. In this Review, we discuss how the synergy between inflammation and thrombosis drives thrombotic diseases. We focus on the huge potential of anti-inflammatory strategies to target cardiovascular pathologies. Findings in the past decade have uncovered a sophisticated connection between innate immunity, platelet activation and coagulation, termed immunothrombosis. Immunothrombosis is an important host defence mechanism to limit systemic spreading of pathogens through the bloodstream. However, the aberrant activation of immunothrombosis in cardiovascular diseases causes myocardial infarction, stroke and venous thromboembolism. The clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is supported by the increased risk of cardiovascular events in patients with inflammatory diseases but also during infections, including in COVID-19. Clinical trials in the past 4 years have confirmed the anti-ischaemic effects of anti-inflammatory strategies, backing the concept of a prothrombotic function of inflammation. Targeting inflammation to prevent thrombosis leaves haemostasis mainly unaffected, circumventing the risk of bleeding associated with current approaches. Considering the growing number of anti-inflammatory therapies, it is crucial to appreciate their potential in covering therapeutic gaps in cardiovascular diseases.
血栓形成是心血管疾病最令人恐惧的并发症，也是全球死亡的主要原因，因此它是一个主要的医疗保健挑战。抗血栓形成方法有效地针对血小板和凝血级联反应，但存在出血的固有风险。此外，抗血栓药物不能完全预防血栓事件，这表明由于第三个尚未充分解决的机制，即炎症，存在治疗空白。在这篇综述中，我们讨论了炎症和血栓形成之间的协同作用如何驱动血栓形成性疾病。我们专注于抗炎策略靶向心血管疾病的巨大潜力。过去十年的研究结果揭示了固有免疫、血小板激活和凝血之间复杂的联系，称为免疫血栓形成。免疫血栓形成是一种重要的宿主防御机制，可通过血液限制病原体的全身传播。然而，心血管疾病中免疫血栓形成的异常激活导致心肌梗死、中风和静脉血栓栓塞。炎症性疾病患者心血管事件风险增加，以及感染期间（包括 COVID-19 期间）的风险增加，支持了异常免疫血栓形成（称为血栓炎症）的临床相关性。过去 4 年的临床试验证实了抗炎策略的抗缺血作用，支持了炎症具有促血栓形成功能的概念。针对炎症预防血栓形成主要不会影响止血，避免了与当前方法相关的出血风险。考虑到越来越多的抗炎治疗方法，了解它们在填补心血管疾病治疗空白方面的潜力至关重要。
