Immunohistological Evaluation of Von Willebrand Factor in the Left Atrial Endocardium and Atrial Thrombi from Cats with Cardiomyopathy

SIMPLE SUMMARY: Disease of the heart muscle (cardiomyopathy) is very common in the domestic cat and may result in several severe outcomes. These include formation of a thrombus in the left atrium which migrates to the hindlimb cutting off the blood supply, a condition called aortic thromboembolism. Affected cats present with hindlimb paralysis and extreme pain, often requiring euthanasia on humane grounds. Several factors are known to predispose to thrombus formation, including damage to the inner cellular lining of the atrium which exposes proteins that initiates thrombosis. We studied the expression of one such protein called von Willebrand Factor in the left atrium of cats with and without cardiomyopathies and at different stages of disease severity. We found that expression increased in cats with advance disease. Obtaining a greater understanding of the role this protein has in thrombus formation may allow development of novel antithrombotic agents to help prevent this devastating consequence of feline cardiomyopathy. ABSTRACT: 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.