HDAC6 regulates endothelial dysfunction in thromboembolic venous disease
National Institute of Health and Medical Research (INSERM)
Endothelial-to-mesenchymal transition (EndMT) is a type of endothelial dysfunction involved in cardiovascular disease. It is characterized by the loss of endothelial markers and acquisition of mesenchymal markers and may lead to fibrosis. Fibrosis might be involved in recurrence of venous thromboembolism (VTE). The transforming growth factor (TGFβ), an anti-fibrotic cytokine, is the most potent inducer of EndMT. Recent data showed that in chronic thromboembolic pulmonary hypertension, TGFβ induces the EndMT, altering thrombus resolution. However, the molecular mechanism involved in EndMT in the context of VTE is unknown. Pilard presents new data focusing on how histone deacetylase 6 (HDAC) might regulate TGFβ signaling pathway in endothelial cells promoting EndMT and VTE recurrence. More precisely, inhibition of HDAC6 siRNA reduced expression of the mesenchymal markers, calponin and α-smooth muscle actin. Moreover, after a first event of thrombosis, thrombus resolution appears to be accelerated in the presence of HDAC6 inhibitor.