Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Renal ischemia reperfusion injury (IRI) is a major contributor to early allograft dysfunction (EAD) in kidney transplantation. We previously identified lower rates of EAD among female renal transplant recipients in the UNOS registry. Using a murine model, we demonstrated improved IRI tolerance with administration of supplemental 17β-estradiol (E2). We also identified decreased ischemia tolerance in estrogen receptor α knockout (ERα-KO) mice. Given the therapeutic potential of E2 in renal transplantation, further clarification of E2’s mechanism of action is essential. As E2 is an agonist of both ERα and estrogen receptor β (ERβ), we aim to clarify the role that ERβ plays in estrogen-mediated IRI tolerance using whole-body ERβ knockout (ERβ-KO) and selective estrogen receptor β deletion in the vascular endothelium (Tie2-Cre (+) ERβ-/-).
*Methods: In two separate experiments, female ERβ-KO mice and Tie2-Cre (+) ERβ-/- mice were subjected to temperature-controlled renal ischemia along with female, wild-type C57BL/6 (B6) controls. Blood urea nitrogen (BUN) and serum creatinine (Cr) were measured at 24, 48, 72, and 96 hours after surgery.
*Results: ERβ-KO mice demonstrated significantly lower BUN (p<0.0001) and Cr (p=0.0013) compared to B6 mice (Figure 1). Similarly, Tie2-Cre (+) ERβ-/- mice portrayed significantly lower BUN (p<0.001) and Cr (p=0.03) compared to B6 mice (Figure 2).
*Conclusions: Whole-body ERβ-KO is protective in warm renal IRI, and selective deletion of ERβ from the vascular endothelium is sufficient to generate the protective phenotype seen in the whole-body knockout. These previously unreported findings suggest that signaling via ERα and ERβ may have opposite effects on ischemia tolerance in renal IRI. Further investigation into the different roles that these receptors play in renal IRI will help direct the development of selective and clinically useful interventions.
To cite this abstract in AMA style:Krumeich L, Hernandez P, O'Brien C, Concors S, Wang Z, Ge G, Hancock W, Levine M. Estrogen Receptor Beta Deletion in the Vascular Endothelium is Protective in Renal Ischemia Reperfusion Injury [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/estrogen-receptor-beta-deletion-in-the-vascular-endothelium-is-protective-in-renal-ischemia-reperfusion-injury/. Accessed August 7, 2020.
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