Interplay Among Endothelial Dysfunction, NLRP3 Pathway Activation, and microRNAs in the Pathogenesis of Preeclampsia

Figure 1. NLRP3 inflammasome activation and regulatory mechanisms in preeclampsia (PE). The NLRP3 activation occurs in two steps: priming and activation. Priming, mediated by PRRs and inflammatory cytokines, induces NF-κB–dependent upregulation of NLRP3 and pro–IL-1β. Activation is triggered by PE-associated cellular stress signals. These events promote assembly of the NLRP3 inflammasome complex (NLRP3, ASC, and pro–caspase-1—represented by the elements rose yellow—caspase-1, yellow green and blue—ASC, and green and blue—NLRP) leading to caspase-1 activation, IL-1β and IL-18 maturation, and gasdermin D–mediated pyroptosis. NLRP3 activity is regulated by mechanisms such as post-translational modifications, autophagy, nitric oxide signaling, and miRNA-mediated repression. Dysregulation of these pathways may contribute to inflammation and endothelial dysfunction in PE. Graphical elements were adapted from Servier Medical (https://smart.servier.com/, accessed between 1 December 2025 and 1 March 2026), licensed under CC BY 4.0 and created using Canva (https://www.canva.com/, accessed between 1 December 2025 and 1 March 2026).

Figure 2. Example of possible miRNA-mediated regulation of the NLRP3 inflammasome in preeclampsia (PE). In the preeclamptic placenta, hypoxia, oxidative stress, and the release of DAMPs and extracellular vesicles containing dysregulated miRNAs may contribute to endothelial activation. Altered miRNA expression is capable of disrupting post-transcriptional regulation of inflammasome components and upstream signaling pathways, promoting NLRP3 priming and activation. This leads to caspase-1 activation, IL-1β and IL-18 release, endothelial inflammation, and endothelial dysfunction, contributing to PE progression. Graphical elements were adapted from Servier Medical (https://smart.servier.com/, accessed between 1 December 2025 and 1 March 2026), licensed under CC BY 4.0 and created using Canva (https://www.canva.com/, accessed between 1 December 2025 and 1 March 2026).