@misc{10481/106417,
year = {2025},
month = {11},
url = {https://hdl.handle.net/10481/106417},
abstract = {Hypertension (HTN) is a prominent cardiovascular risk factor frequently observed in patients with systemic lupus
erythematosus (SLE). This study explores whether pharmacological interventions targeting dysfunctional immune cell metabolism can confer vascular protection in a genetic mouse model of SLE. Female NZBWF1 lupus
mice, aged 29 weeks, were treated for 4 weeks with either a vehicle (SLE group), a combination of 2-deoxy-Dglucose (2DG) and metformin (Met), or rapamycin. NZW/LacJ mice served as controls. The treatment with 2DG
+ Met inhibited splenic glycolysis and mitochondrial metabolism, enhanced AMP-activated protein kinase
(AMPK) activity, and suppressed mammalian target of rapamycin (mTOR) activity. These effects resulted in a
reduction in activated T helper (Th) cells and Th17 cells. The treatment managed to prevent the onset of HTN
and ameliorated aortic dysfunction, as evidenced by reduced vascular contraction to the thromboxane A2 receptor agonist U46619, improved endothelium-dependent relaxation to acetylcholine, and attenuation of
vascular thickening along with diminished collagen and proteoglycan accumulation. This intervention also
decreased aortic Th17 cell infiltration in SLE mice, mitigating the profibrotic, proinflammatory, and oxidative
stress within the vasculature, primarily via the IL-17/Rho kinase/NADPH oxidase and Rho kinase/serum
response factor/myocardin pathways. Moreover, the activation of AMPK in the vascular wall by 2DG + Met
improved endothelial dysfunction. Similarly, rapamycin suppressed splenic mTORC1 activity, reducing Th17
differentiation and aortic Th17 infiltration, which subsequently alleviated vascular oxidative stress and endothelial dysfunction. In conclusion, immune metabolic modulators improved vascular abnormalities in SLE mice,
highlighting the potential therapeutic applications of these interventions in hypertensive SLE patients.},
organization = {MCIN/AEI /10.13039/
501100011033 (Ref. PID2020-116347RB-I00)},
organization = {Junta de Andalucía (CTS 164, P20_00193, A-CTS318-UGR20)},
organization = {Instituto de Salud Carlos III (PI22/
01046, PI23/00734, CIBER-CV)},
organization = {Fondo Europeo de Desarrollo Regional - FEDER},
publisher = {Elsevier},
keywords = {Glycolysis},
keywords = {Mitochondrial metabolism},
keywords = {Hypertension},
title = {Immunometabolic modulators alleviate vascular dysfunction in mice with systemic lupus erythematosus},
doi = {10.1016/j.bcp.2025.117154},
author = {Miñano, Sofía and Moleón Moya, Javier and González-Correa, Cristina and Jiménez Moleón, Rosario and Gómez-Guzmán, Manuel and Martín-Morales, Natividad and O´Valle, Francisco and Romero Pérez, Miguel and Toral, Marta and Duarte Pérez, Juan Manuel},
}