Intact NOX2 in T Cells Mediates Pregnancy-Induced Renal Damage in Dahl SS Rats.

Autor:	Dasinger JH; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Abais-Battad JM; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Walton SD; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Burns-Ray EC; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Cherian-Shaw M; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Baldwin KE; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.)., Fehrenbach DJ; Department of Medicine, Indiana University School of Medicine, Indianapolis (D.J.F.)., Mattson DL; Department of Physiology, Medical College of Georgia, Augusta University (J.H.D., J.M.A.-B., S.D.W., E.C.B.-R., M.C.-S., K.E.B., D.L.M.).
Jazyk:	angličtina
Zdroj:	Hypertension (Dallas, Tex. : 1979) [Hypertension] 2024 Nov; Vol. 81 (11), pp. 2357-2367. Date of Electronic Publication: 2024 Sep 20.
DOI:	10.1161/HYPERTENSIONAHA.124.23303
Abstrakt:	Background: Hypertensive disorders of pregnancy are associated with increased risk for cardiovascular disease, renal disease, and mortality. While the exact mechanisms remain unclear, T cells and reactive oxygen species have been implicated in its pathogenesis. We utilized Dahl salt-sensitive (SS), SS CD247-/- (Dahl SS CD247 knockout rat; lacking T cells), and SS p67phox-/- (Dahl SS p67 phox [NOX2 (NADPH [nitcotinamide adenine dinucleotide phosphate] oxidase 2)] knockout rat; lacking NOX2) rats to investigate these mechanisms in primigravida and multigravida states. Methods: We assessed blood pressure and renal damage phenotypes in SS, SS CD247-/- , and SS p67phox-/- rats during primigravida and multigravida states. To investigate the contribution of NOX2 in T cells, we performed adoptive transfers of splenocytes or cluster of differentiation (CD)4 + T cells from either SS or SS p67phox-/- donors into SS CD247-/- recipients to determine pregnancy-specific alterations in phenotype. Results: Multigravida SS rats developed significant pregnancy-induced renal damage and renal functional impairment associated with elevated maternal mortality rates, whereas deletion of T cells or NOX2 garnered protection. During primigravida states, this attenuation in renal damage was observed, with the greatest protection in the SS p67phox-/- rat. To demonstrate that NOX2 in T cells contributes to adverse pregnancy phenotypes, adoptive transfer of SS splenocytes into SS CD247-/- rats resulted in significant pregnancy-induced renal damage, whereas transfer of SS p67phox-/- splenocytes garnered protection. Specifically, the transfer of SS CD4 + T cells resulted in pregnancy-induced proteinuria and increases in uterine artery resistance index, an effect not seen with the transfer of SS p67phox-/- CD4 + T cells. Conclusions: T cells and NOX2-derived reactive oxygen species, thus, contribute to end-organ damage in both primigravida and multigravida pregnancies in the SS rat leading to increases in maternal mortality. Competing Interests: None.
Databáze:	MEDLINE
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