Coronary microthrombi in the failing human heart: the role of von Willebrand factor and PECAM-1

Abstract

The recognition of microthrombi in the heart microcirculation has recently emerged from studies in COVID-19 decedents. The present study investigated the ultrastructure of coronary microthrombi in heart failure (HF) due to cardiomyopathies that are unrelated to COVID-19 infection. In addition, we have investigated the role of von Willebrand factor (VWF) and PECAM-1 in microthrombus formation. We used electron microscopy to investigate the occurrence of microthrombi in patients with HF due to dilated (DCM, n = 7), inflammatory (MYO, n = 6) and ischemic (ICM, n = 7) cardiomyopathy and 4 control patients. VWF and PECAM-1 was studied by quantitative immunohistochemistry and Western blot. In comparison to control, the number of microthrombi was increased 7–9 times in HF. This was associated with a 3.5-fold increase in the number of Weibel–Palade bodies (WPb) in DCM and MYO compared to control. A fivefold increase in WPb in ICM was significantly different from control, DCM and MYO. In Western blot, VWF was increased twofold in DCM and MYO, and more than threefold in ICM. The difference between ICM and DCM and MYO was statistically significant. These results were confirmed by quantitative immunohistochemistry. Compared to control, PECAM-1 was by approximatively threefold increased in all groups of patients. This is the first study to demonstrate the occurrence of microthrombi in the failing human heart. The occurrence of microthrombi is associated with increased expression of VWF and the number of WPb, being more pronounced in ICM. These changes are likely not compensated by increases in PECAM-1 expression.