Neuraminidase-3 Overexpression Impairs Endothelial Function and Elevates Blood Pressure in Mice

Neuraminidases (Neu) are glycosidases responsible for cleaving sialic acid residues. In the vasculature, Neu activity reduces the endothelial glycocalyx, a known mechanosensor of blood flow-induced shear stress. Increased plasma Neu activity is associated with endothelial dysfunction and reduced arterial flow-mediated dilation (FMD) in conditions such as type 2 diabetes and hypertension. However, the specific contribution of individual Neu isoforms remains unclear. The mammalian Neu enzyme family consists of four members of which Neu3 is the most abundant in plasma. Therefore, we hypothesized that Neu3 overexpressing (OE) mice exhibit endothelial dysfunction and increased blood pressure. Consistent with this hypothesis, we found that Neu3-OE mice exhibit a significant increase in mean arterial pressure as assessed by tail cuff. Endothelium-dependent relaxation in response to acetylcholine was impaired in aortic rings from Neu3-OE mice, as was FMD in mesenteric resistance arteries, while endothelium-independent vasodilation in response to sodium nitroprusside was unaffected. These findings indicate that Neu3 activity can lead to endothelial dysfunction and hypertension. Further studies should determine whether Neu3 inhibition is a viable strategy to ameliorate cardiovascular disease. LM-L and JP are supported by the National Institutes of Health grant: R01HL153264. FIR-P is supported by the Research Excellence Program at the University of Missouri. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.