Figure 2.

Inflammasome action in the lung vascular environment. Immune cells (such as macrophages) and non-immune cells (endothelial cells) can respond to stress, activate the inflammasome pathway and undergo pyroptosis. The release of pro-inflammatory cytokines through the GSDMD pore, such as IL-1B, can propagate inflammation in neighboring cells by inducing their own transcription in a paracrine fashion. As such, the innate immune response can be amplified through the lung vasculature. In addition, these activated cells can (1) release other potent signaling molecules, such as HMGB1, into the environment following lytic cell death, (2) increase smooth muscle cell (SMC) proliferation in the medial layer of the vessel, and (3) release cytokines such as IL-6 that recruit other inflammatory cells to the vessel wall. Overall, this creates a vicious inflammatory cycle that, over time, contributes to the characteristic pulmonary vascular remodeling seen in PAH patients.