NETs Activate Pulmonary Arterial Endothelial Cells
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The article by Aldabbous et al1 describes neutrophil extracellular traps (NETs) as a novel feature related to the vascular pathology of both pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). NETs were originally identified as a suicide mechanism whereby neutrophil elastase degrades and releases chromatin to trap bacteria. In this article, the authors first describe biomarkers of NETs, that is, elevated circulating levels of neutrophil elastase, myeoloperoxidase, citrullinated histone 3, and DNA in PAH and CTEPH patients. Moreover, they found neutrophils, the primary source of NETs, characterized by elevated peptidylarginine deiminase 4+ in and around occlusive arterial lesions in PAH and CTEPH lungs.
See accompanying article on page 2078
The release of neutrophil elastase in association with NETs is thought to produce collateral tissue damage2 as reported in other vascular pathologies, notably aneurysm formation3 and atherosclerosis.4 Neutrophil elastase, in particular, has been implicated in the pathogenesis of PAH, by releasing of growth factors from the extracellular matrix and activating growth factor receptors, by initiating an elastin peptide mediated inflammatory response and by inducing vascular stiffening.5 Moreover, elastase inhibitors can prevent and reverse experimental pulmonary hypertension and PA occlusive lesions in human tissue.6 NETs are generally ingested by scavenging cells, such as MMP12 (matrix metalloproteinase)-producing macrophages, unless the function of those cells is compromised …