Pulmonary Vascular Signaling in Pulmonary Hypertension: Potential Role of Endothelial Ca2+ Signaling in Cellular Senescence and Inflammasome Activation - PubMed
7 hours ago
- #pulmonary hypertension
- #vascular remodeling
- #endothelial signaling
- Endothelial Ca2+ and K+ signaling may play pathogenic roles in pulmonary hypertension by regulating cellular senescence and inflammasome activation.
- Ca2+ influx and release in lung vascular endothelial cells upregulate cell cycle inhibitors (p53, p21, p16) via the AKT/mTORC1 pathway, leading to cellular senescence.
- Increased cytosolic Ca2+ activates both canonical (NLRP3) and noncanonical inflammasomes, promoting vascular and perivascular inflammation.
- K+ efflux through various channels/pores (e.g., K+ ionophores, Ca2+-activated K+ channels) is sufficient for NLRP3 inflammasome activation.
- Senescent endothelial cells release senescence-associated secretory phenotype (SASP) factors, inducing endothelial-to-mesenchymal transition and smooth muscle cell proliferation, contributing to vascular remodeling and pulmonary hypertension.