Publications by authors named "W el-Khoury"
Vascular inflammation regulates endothelial pathophenotypes, particularly in pulmonary arterial hypertension (PAH). Dysregulated lysosomal activity and cholesterol metabolism activate pathogenic inflammation, but their relevance to PAH is unclear. Nuclear receptor coactivator 7 () deficiency in endothelium produced an oxysterol and bile acid signature through lysosomal dysregulation, promoting endothelial pathophenotypes.
View Article and Find Full Text PDFPost-transcriptional regulation of IFI16 promotes inflammatory endothelial pathophenotypes observed in pulmonary arterial hypertension.
Am J Physiol Lung Cell Mol Physiol
January 2025
Article Synopsis
- Pulmonary arterial hypertension (PAH) is a disease caused by inflammation and dysfunction in blood vessel cells, leading to changes in the lungs' blood vessels.
- The study highlights the role of the protein IFI16 in promoting inflammation in these endothelial cells, especially when triggered by the inflammatory molecule IL-1b.
- Additionally, the research suggests that changes in m6A modification of IFI16 may serve as a potential biomarker for identifying PAH in patients, as increased m6A levels were found in their blood cells compared to healthy controls.
Pulmonary arterial hypertension (PAH) is a progressive disease driven by endothelial cell inflammation and dysfunction, resulting in the pathological remodeling of the pulmonary vasculature. Innate immune activation has been linked to PAH development; however, the regulation, propagation, and reversibility of the induction of inflammation in PAH is poorly understood. Here, we demonstrate a role for interferon inducible protein 16 (IFI16), an innate immune sensor, as a modulator of endothelial inflammation in pulmonary hypertension, utilizing human pulmonary artery endothelial cells (PAECs).
View Article and Find Full Text PDFArticle Synopsis
- Vascular inflammation plays a key role in regulating the behavior of endothelial cells, which is especially significant in pulmonary arterial hypertension (PAH), showing complex connections to lysosomal activity and cholesterol metabolism.
- Research identified that the nuclear receptor coactivator 7 (NCOA7) helps maintain lysosomal function and limits inflammation in endothelial cells; when NCOA7 is deficient, it leads to inflammation and worsened PAH symptoms.
- A genetic variant in NCOA7 was linked to PAH severity and mortality, while a computationally designed drug that activates NCOA7 showed potential in reversing PAH symptoms in mice, highlighting a new therapeutic approach.
Article Synopsis
- The study explores how hypoxia affects blood vessel behavior in pulmonary arterial hypertension (PAH) through a genetic and epigenetic mechanism involving HIF-2α.
- HIF-2α enhances the expression of certain genes and long noncoding RNAs that contribute to increased vascular dysfunction, creating a feedback loop that further boosts HIF-2α activity.
- A specific genetic variant (rs73184087) is linked to an increased risk of PAH; interventions that either inhibit this pathway or reduce HIF-2α levels showed protective effects against the disease in animal models.