Cheng Wan-Ching, Wilkie Lois, Kurosawa Tsumugi Anne, Dobromylskyj Melanie, Priestnall Simon Lawrence, Luis Fuentes Virginia, Connolly David J
Department of Clinical Science and Services, Royal Veterinary College, Hawkshead Lane, North Mymms, Hatfield AL9 7TA, UK.
Finn Pathologists, 3c, 3 Mayflower Way, Harleston IP20 9EB, UK.
Animals (Basel). 2021 Apr 26;11(5):1240. doi: 10.3390/ani11051240.
Aortic thromboembolism (ATE) occurs in cats with cardiomyopathy and often results in euthanasia due to poor prognosis. However, the underlying predisposing mechanisms leading to left atrial (LA) thrombus formation are not fully characterised. von Willebrand Factor (vWF) is a marker of endothelium and shows increased expression following endothelial injury. In people with poor LA function and LA remodelling, vWF has been implicated in the development of LA thrombosis. In this study we have shown (1) the expression of endocardial vWF protein detected using immunohistofluorescence was elevated in cats with cardiomyopathy, LA enlargement (LAE) and clinical signs compared to cats with subclinical cardiomyopathy and control cats; (2) vWF was present at the periphery of microthrombi and macrothrombi within the LA where they come into contact with the LA endocardium and (3) vWF was integral to the structure of the macrothrombi retrieved from the atria. These results provide evidence for damage of the endocardial endothelium in the remodelled LA and support a role for endocardial vWF as a pro-thrombotic substrate potentially contributing to the development of ATE in cats with underlying cardiomyopathy and LAE. Results from this naturally occurring feline model may inform research into human thrombogenesis.
主动脉血栓栓塞（ATE）发生于患有心肌病的猫，且由于预后不良常导致实施安乐死。然而，导致左心房（LA）血栓形成的潜在诱发机制尚未完全明确。血管性血友病因子（vWF）是内皮细胞的标志物，在内皮损伤后表达增加。在左心房功能不良和左心房重塑的人群中，vWF与左心房血栓形成有关。在本研究中，我们发现：（1）与患有亚临床心肌病的猫和对照猫相比，使用免疫荧光检测到的心内膜vWF蛋白在患有心肌病、左心房扩大（LAE）和有临床症状的猫中表达升高；（2）在左心房内微血栓和大血栓与左心房心内膜接触的周边部位存在vWF；（3）vWF是从心房取出的大血栓结构的组成部分。这些结果为重塑的左心房内心内膜内皮损伤提供了证据，并支持心内膜vWF作为促血栓形成底物的作用，可能促使患有潜在心肌病和左心房扩大的猫发生ATE。这个自然发生的猫科动物模型的结果可能为人类血栓形成的研究提供参考。
