Endothelial Dysfunction in Pulmonary Hypertension: Cause or Consequence?

Pulmonary arterial hypertension (PAH) is a rare, complex, and progressive disease that is characterized by the abnormal remodeling of the pulmonary arteries that leads to right ventricular failure and death. Although our understanding of the causes for abnormal vascular remodeling in PAH is limited, accumulating evidence indicates that endothelial cell (EC) dysfunction is one of the first triggers initiating this process. EC dysfunction leads to the activation of several cellular signalling pathways in the endothelium, resulting in the uncontrolled proliferation of ECs, pulmonary artery smooth muscle cells, and fibroblasts, and eventually leads to vascular remodelling and the occlusion of the pulmonary blood vessels. Other factors that are related to EC dysfunction in PAH are an increase in endothelial to mesenchymal transition, inflammation, apoptosis, and thrombus formation. In this review, we outline the latest advances on the role of EC dysfunction in PAH and other forms of pulmonary hypertension. We also elaborate on the molecular signals that orchestrate EC dysfunction in PAH. Understanding the role and mechanisms of EC dysfunction will unravel the therapeutic potential of targeting this process in PAH.

Automated summary

This review highlights the crucial role of endothelial cell dysfunction in pulmonary arterial hypertension (PAH) and its contribution to the progression of the disease. The activation of various cellular signaling pathways due to endothelial cell dysfunction ultimately leads to pulmonary artery remodeling and occlusion. Understanding the molecular signals orchestrating endothelial cell dysfunction in PAH is essential for exploring therapeutic interventions targeting this process.