Key result
Let-7b-5p mimic improves survival and reduces aortic dissection incidence in mice.
Why the study?
Vascular smooth muscle cell loss and PANoptosis drive medial degeneration in aortic dissection, but the specific contribution of the microRNA let-7b-5p to VSMC PANoptosis and aortic dissection pathogenesis remained poorly defined.
Does subcutaneous administration of let-7b-5p mimics improve survival and reduce aortic dissection incidence by suppressing VSMC PANoptosis in a murine model of aortic dissection?
Does subcutaneous administration of let-7b-5p mimics improve survival and reduce aortic dissection incidence by suppressing VSMC PANoptosis in a murine model of aortic dissection?
Answers are grounded in this paper and cite their sources.
In a murine model, subcutaneous delivery of let-7b-5p mimics protects against aortic dissection and improves survival by inhibiting inflammatory vascular smooth muscle cell PANoptosis.
Background Vascular smooth muscle cell (VSMC) loss is a hallmark of aortic dissection (AD) pathogenesis. Emerging evidence suggests that PANoptosis, a unique inflammatory cell death mechanism involving apoptosis, necroptosis, and pyroptosis, drives medial degeneration. While microRNAs are essential post-transcriptional regulators, the specific contribution of let-7b-5p to VSMC PANoptosis and AD pathogenesis remains poorly defined. Purpose This study aimed to investigate whether let-7b-5p protects aortic integrity by modulating PANoptotic signaling. Methods AD was induced in mice using β-aminopropionitrile fumarate (BAPN) and Angiotensin II (Ang II). To assess therapeutic efficacy, mice were administered subcutaneously with let-7b-5p mimics or negative controls. Survival rates, AD incidence, and vascular morphology (H&E, EVG staining) were evaluated. The expression of PANoptotic executioners (CASP3, NLRP3, and MLKL) was quantified in the aortic media. Results In murine AD models, let-7b-5p expression was significantly downregulated, correlating with a robust increase in CASP3, NLRP3, and MLKL within the medial layer. Restoration of let-7b-5p significantly improved animal survival and decreased AD incidence. Histological analysis revealed that let-7b-5p overexpression markedly attenuated elastic fiber breakage, pseudolumen formation, and inflammatory cell infiltration. Furthermore, let-7b-5p delivery effectively suppressed the activation of PANoptosis-related markers in the aortic wall, preserving the VSMC population and structural stability. Conclusions Our findings identify let-7b-5p as a novel protective regulator that safeguards the aorta by suppressing VSMC PANoptosis. These results suggest that targeting the let-7b-5p axis may offer a potent therapeutic strategy to limit pathological remodeling and preventing AD.Scheme
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Lu et al. (2026) studied Aortic dissection. let-7b-5p mimics vs. Negative controls was evaluated on Survival rates, aortic dissection incidence, vascular morphology, and PANoptotic executioner expression (CASP3, NLRP3, MLKL). Subcutaneous let-7b-5p mimic administration significantly improved survival, reduced aortic dissection incidence, and suppressed medial CASP3, NLRP3, and MLKL expression in mice.
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