Buchumschlag

Sex-specific protection of endothelial function after vascular ischemia/reperfusion injury by the senomorphic agent Ruxolitinib

Ischemia/reperfusion (I/R)-induced endothelial dysfunction occurs in various cardiovascular disorders. I/R injury is partially driven by the release of cytokines. Known for its use in senotherapy, the JAK inhibitor ruxolitinib is able to block the release of cytokines. We investigated the effect of...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Saemann, Lars (VerfasserIn) , Naujoks, Paula (VerfasserIn) , Hartrumpf, Lotta (VerfasserIn) , Pohl, Sabine (VerfasserIn) , Simm, Andreas (VerfasserIn) , Szabó, Gábor (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 2023
In: International journal of molecular sciences
Year: 2023, Jahrgang: 24, Heft: 14, Pages: 1-15
ISSN:1422-0067
DOI:10.3390/ijms241411727
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.3390/ijms241411727
Verlag, kostenfrei, Volltext: https://www.mdpi.com/1422-0067/24/14/11727
Volltext
Verfasserangaben:Lars Saemann, Paula Naujoks, Lotta Hartrumpf, Sabine Pohl, Andreas Simm and Gábor Szabó
Beschreibung
Zusammenfassung:Ischemia/reperfusion (I/R)-induced endothelial dysfunction occurs in various cardiovascular disorders. I/R injury is partially driven by the release of cytokines. Known for its use in senotherapy, the JAK inhibitor ruxolitinib is able to block the release of cytokines. We investigated the effect of ruxolitinib on the cytokine release and endothelial-dependent vasorelaxation in an in vitro model of I/R. Aortic segments of C57BL/6J mice (N = 12/group) were divided into three groups: control, in vitro I/R (I/R group), and in vitro I/R with ruxolitinib during ischemic incubation (I/R+Ruxo group). We determined cytokine expression. In organ bath chambers, we investigated the maximal endothelial-dependent relaxation to acetylcholine (RmaxACh) and maximal endothelial-independent relaxation to sodium-nitroprusside (RmaxSNP). RmaxACh was decreased in I/R compared to the control (83.6 ± 2.4 vs. 48.6 ± 3.4%; p < 0.05) and I/R+Ruxo (74.4 ± 2.6 vs. 48.6 ± 3.4%; p < 0.05). RmaxSNP was comparable between all groups. IL-10 was detectable only in I/R+Ruxo. CXCL5, CCL2, CCL3, CCL8, CCL11, ICAM-1, IL-1α, IL-7, TNF-α, and G-CSF were decreased or not detectable in I/R+Ruxo. In I/R+Ruxo, ICAM-1 was reduced in rings only from male mice. Treatment of the aorta from mice during in vitro ischemia with the senomorphic agent ruxolitinib reduces cytokine release and protects the endothelium from I/R-mediated dysfunction.
Beschreibung:Veröffentlicht: 21. Juli 2023
Gesehen am 24.08.2023
Beschreibung:Online Resource
ISSN:1422-0067
DOI:10.3390/ijms241411727

Ähnliche Einträge