SSc-PAH Patients Demonstrate Endothelial-to-Mesenchymal Transition

It is widely accepted that hypertrophic mesenchymal stem cells contribute to pulmonary arterial hypertension (PAH) in individuals with systemic sclerosis (SSc). Now, as a result of a study presented at the 2014 American College of Rheumatology Meeting, scientists have reason to believe that endothelial cells can increase the pool of mesenchymal cells and further contribute to SSc-PAH.

Dr. Robert Good from the Rheumatology and Connective Tissue Diseases Department at University College London (UCL), presented work entitled “Endothelial to Mesenchymal Transition Contributes to the Development of Pulmonary Vasculopathy in Systemic Sclerosis PAH,” that suggests endothelial cells can become mesenchymal-like and contribute to the growing population of mesenchymal cells. The research team at UCL quantified the prevalence of the switch, known as the endothelial-mesenchymal transition (EndoMT), in SSc-PAH patients, in vivo mouse models of PAH, and in vitro cell culture models of PAH.

An equal number of lung tissue samples from SSc-PAH patients and healthy donors were analyzed for co-expression of von Willebrand factor (an endothelial marker) and α-smooth muscle actin (a mesenchymal marker). The two proteins overlapped, and this result was replicated when the researchers analyzed lung tissue from PAH mice.

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When the researchers induced EndoMT in human pulmonary arterial endothelial cells (PAECs) in vitro, they saw morphological changes in the PAECs. The PAECs also lost endothelial markers and gained mesenchymal markers within six days of induction. These EndoMT cells produced higher levels of pro-inflammatory cytokines than normal PAECs and were more permeable than normal. “EndoMT cells failed to form integral biological barriers and contributed to enhanced permeability of PAEC barriers,” noted the researchers.

Considering the results of the study, the authors stated, “Collectively our data suggests that EndoMT may contribute to the loss of normal endothelium function and the development of SSc-PAH.” If there was a way to monitor this transition, clinicians and patients may be more aware of a potential diagnosis of SSc-PAH and be able to slow its progression if appropriate treatment options exist, such as drugs that target inflammation in PAH.