Abnormal pulmonary endothelial cells may underlie the enigmatic pathogenesis of chronic thromboembolic pulmonary hypertension

作者：Mercier Olaf; Ataam Jennifer Arthur; Langer Nathaniel B; Dorfmueller Peter; Lamrani Lilia; Lecerf Florence; Decante Benoit; Dartevelle Philippe; Eddahibi Saadia; Fadel Elie

来源：Journal of Heart and Lung Transplantation, 2017, 36(3): 305-314.

DOI：10.1016/j.healun.2016.08.012

• chronic thromboembolic pulmonary hypertension
• venous thromboembolism
• pulmonary artery endothelial cells
• growth factors
• cytokine signaling
• adhesion molecules
• pathogenesis

BACKGROUND: Chronic thromboembolic pulmonary hypertension results from chronic mechanical obstruction of the pulmonary arteries after acute venous-thromboembolism. However, the mechanisms that result in the progression from unresolved thrombus to fibrotic vascular remodeling are unknown. We hypothesized that pulmonary artery endothelial cells contribute to this phenomenon via paracrine growth factor and cytokine signaling.
METHODS: Using enzyme-linked immunosorbent assay and cell migration assays, we investigated the circulating growth factors and cytokines of chronic thromboembolic pulmonary hypertension patients as well as the cross talk between pulmonary endothelial cells and pulmonary artery smooth muscle cells and monocytes from patients with chronic thromboembolic pulmonary hypertension in vitro.
RESULTS: Culture medium from the pulmonary endothelial cells of chronic thromboembolic pulmonary hypertension patients contained higher levels of growth factors (fibroblast growth factor 2), inflammatory cytokines (interleukin 1 beta, interleukin 6, monocyte chemoattractant protein 1), and cell adhesion molecules (vascular cell adhesion molecule 1 and intercellular adhesion molecule 1). Furthermore, exposure to the culture medium of pulmonary endothelial cells from patients with chronic thromboembolic pulmonary hypertension elicited marked pulmonary artery smooth muscle cell growth and monocyte migration.
CONCLUSIONS: These findings implicate pulmonary endothelial cells as key regulators of pulmonary artery smooth muscle cell and monocyte behavior in chronic thromboembolic pulmonary hypertension and suggest a potential mechanism for the progression from unresolved thrombus to fibrotic vascular remodeling.

• 出版日期2017-3