| First Author | Miyazaki-Anzai S | Year | 2024 |
| Journal | JCI Insight | Volume | 9 |
| Issue | 7 | PubMed ID | 38470493 |
| Mgi Jnum | J:350694 | Mgi Id | MGI:7664327 |
| Doi | 10.1172/jci.insight.174977 | Citation | Miyazaki-Anzai S, et al. (2024) Activation of the IKK2/NF-kappaB pathway in VSMCs inhibits calcified vascular stiffness in CKD. JCI Insight 9(7) |
| abstractText | IKK2/NF-kappaB pathway-mediated inflammation in vascular smooth muscle cells (VSMCs) has been proposed to be an etiologic factor in medial calcification and stiffness. However, the role of the IKK2/NF-kappaB pathway in medial calcification remains to be elucidated. In this study, we found that chronic kidney disease (CKD) induces inflammatory pathways through the local activation of the IKK2/NF-kappaB pathway in VMSCs associated with calcified vascular stiffness. Despite reducing the expression of inflammatory mediators, complete inhibition of the IKK2/NF-kappaB pathway in vitro and in vivo unexpectedly exacerbated vascular mineralization and stiffness. In contrast, activation of NF-kappaB by SMC-specific IkappaBalpha deficiency attenuated calcified vascular stiffness in CKD. Inhibition of the IKK2/NF-kappaB pathway induced cell death of VSMCs by reducing anti-cell death gene expression, whereas activation of NF-kappaB reduced CKD-dependent vascular cell death. In addition, increased calcification of extracellular vesicles through the inhibition of the IKK2/NF-kappaB pathway induced mineralization of VSMCs, which was significantly reduced by blocking cell death in vitro and in vivo. This study reveals that activation of the IKK2/NF-kappaB pathway in VSMCs plays a protective role in CKD-dependent calcified vascular stiffness by reducing the release of apoptotic calcifying extracellular vesicles. |
