Gestational pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a progressive disease marked by the irreversible pulmonary vascular changes of vasoconstriction, thrombosis, and proliferation of smooth muscle and endothelial cells. The untreated clinical course is characterized by progressive dyspnea and a median survival of less than 3 years. Many of these patients are of child-bearing age; however, pregnancy leads to physiologic changes that are particularly poorly tolerated in PAH, conferring a 30%-56% mortality.

Lentiviral delivery of RNAi for in vivo lineage-specific modulation of gene expression in mouse lung macrophages.

Although RNA interference (RNAi) has become a ubiquitous laboratory tool since its discovery 12 years ago, in vivo delivery to selected cell types remains a major technical challenge. Here, we report the use of lentiviral vectors for long-term in vivo delivery of RNAi selectively to resident alveolar macrophages (AMs), key immune effector cells in the lung. We demonstrate the therapeutic potential of this approach by RNAi-based downregulation of p65 (RelA), a component of the pro-inflammatory transcriptional regulator, nuclear factor κB (NF-κB) and a key participant in lung disease pathogenesis.