Kell Douglas B, Lip Gregory Y H, Pretorius Etheresia
Department of Biochemistry, Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, Crown St, Liverpool L69 7ZB, UK.
The Novo Nordisk Foundation Center for Biosustainability, Technical University of Denmark, Søltofts Plads, Building 220, 2800 Kongens Lyngby, Denmark.
Biomedicines. 2024 Apr 17;12(4):891. doi: 10.3390/biomedicines12040891.
Atrial fibrillation (AF) is a comorbidity of a variety of other chronic, inflammatory diseases for which fibrinaloid microclots are a known accompaniment (and in some cases, a cause, with a mechanistic basis). Clots are, of course, a well-known of atrial fibrillation. We here ask the question whether the fibrinaloid microclots seen in plasma or serum may in fact also be a cause of (or contributor to) the development of AF. We consider known 'risk factors' for AF, and in particular, exogenous stimuli such as infection and air pollution by particulates, both of which are known to cause AF. The external accompaniments of both bacterial (lipopolysaccharide and lipoteichoic acids) and viral (SARS-CoV-2 spike protein) infections are known to stimulate fibrinaloid microclots when added in vitro, and fibrinaloid microclots, as with other amyloid proteins, can be cytotoxic, both by inducing hypoxia/reperfusion and by other means. Strokes and thromboembolisms are also common consequences of AF. Consequently, taking a systems approach, we review the considerable evidence in detail, which leads us to suggest that it is likely that microclots may well have an aetiological role in the development of AF. This has significant mechanistic and therapeutic implications.
心房颤动(AF)是多种其他慢性炎症性疾病的合并症,已知这些疾病伴有纤维蛋白样微血栓形成(在某些情况下,基于机制,微血栓还是病因)。当然,血栓是心房颤动的一个众所周知的特征。我们在此提出一个问题,即血浆或血清中所见的纤维蛋白样微血栓是否实际上也可能是心房颤动发生的原因(或促成因素)。我们考虑了已知的心房颤动“危险因素”,特别是诸如感染和颗粒物空气污染等外源性刺激,已知这两者都会导致心房颤动。已知细菌(脂多糖和脂磷壁酸)和病毒(SARS-CoV-2刺突蛋白)感染的外部伴随物在体外添加时会刺激纤维蛋白样微血栓形成,并且与其他淀粉样蛋白一样,纤维蛋白样微血栓可通过诱导缺氧/再灌注及其他方式具有细胞毒性。中风和血栓栓塞也是心房颤动的常见后果。因此,采用系统方法,我们详细回顾了大量证据,这使我们认为微血栓很可能在心房颤动的发生中具有病因学作用。这具有重要的机制和治疗意义。