Abstract
Pulmonary hypertension is characterized by cellular and structural changes in vascular wall of pulmonary arteries. Intimal thickening, fibrosis, medial hypertrophy, adventitial fibroblast activation involve progenitors cells and fibrocytes. We hypothesized that lysophosphatidic acid (LPA), a bioactive lipid, is implicated in this vascular remodeling. We investigated the rat model of hypoxic pulmonary hypertension. Chronic hypoxic exposure induced increase of serum levels of circulating LPA (21.6 (11.0 – 42.3) μM vs 40.9 (23.4 – 71.7) μM, p=0.037). In addition, we observed perivascular LPA immunohistochemical staining in lungs of hypoxic rats (antibody against LPA provided by L‐Path Inc.), which co‐localized with lysophospholipase D. Serum from the hypoxic group of animals had significantly higher chemoattractant properties towards rat primary lung fibroblasts, and this increase in cell migration could be prevented by the LPA receptor 1 and 3 antagonist, VPC12249. LPA increased also adhesive properties of human pulmonary artery endothelial cells and of human peripheral blood mononuclear cells via the activation LPA receptor (1 or 3). We suggest that chronic hypoxia increases circulating and tissue level of LPA which might induce fibroblast migration and recruitment of mononuclear cells in pulmonary vasculature that contributes to pulmonary vascular remodeling.
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