L. Zhao, M. Xu, A.M. Pfefferkorn, C. Erdogan, H. Schwelberger, P. Wang, P.H. Khedkar, M. Eigen, F.B. Lichtenberger, R. Catar, E.Y. Lai, F. Aigner, P.B. Persson, I.M. Sauer, A. Patzak, and M.I. Ashraf published the paper "Lipocalin-2 Restores Soluble Guanylyl Cyclase-Dependent Dilation of the Afferent Arteriole After Renal Transplantation or Ex Vivo Hypoxia/Reoxygenation in Mice" in Acta Physiologica 2025;241(8): e70077.

This study investigated whether iron-bound lipocalin-2 (holo-rLcn2) can restore soluble guanylyl cyclase (sGC)-mediated microvascular dilation in the kidney after hypoxia/reoxygenation (H/R) and kidney transplantation. Microvascular dysfunction is a key factor in ischemia/reperfusion injury, and sGC activators like cinaciguat lose efficacy after severe hypoxia.
Using isolated mouse afferent arterioles (AAs) and ex vivo kidney perfusion, the researchers tested vascular dilation following H/R and syngeneic kidney transplantation with short (30 min) or prolonged (5.5 h) cold ischemia.

• Key findings include:
• H/R impaired AA dilation, which was preserved by holo-rLcn2 but not by iron-free apo-rLcn2.
• The protective effect of holo-rLcn2 was iron-dependent, as it was reversed by the iron chelator deferoxamine.
• Kidney transplants exhibited reduced AA dilation, particularly after prolonged ischemia, but holo-rLcn2 treatment restored dilation to levels seen with shorter ischemia.
• Ex vivo kidney perfusion confirmed that holo-rLcn2 enhanced cinaciguat-induced vascular relaxation at the organ level.

Overall, the study identifies a novel role for iron-bound rLcn2 in preserving renal vascular function after ischemic injury and transplantation, likely by maintaining iron-dependent vascular mechanisms.