@article{10902/32998,
year = {2024},
url = {https://hdl.handle.net/10902/32998},
abstract = {During resolution of inflammation, specialized proresolving mediators (SPMs), including resolvins, are produced to restore tissue homeostasis. We hypothesized that there might be a dysregulation of SPMs pathways in pathological vascular remodeling and that resolvin D2 (RvD2) might prevent vascular remodeling and contractile and endothelial dysfunction in a model of obesity and hypertension. In aortic samples of patients with or without abdominal aortic aneurysms (AAA), we evaluated gene expression of enzymes involved in SPMs synthesis (ALOXs), SPMs receptors and pro-inflammatory genes. In an experimental model of aortic dilation induced by high fat diet (HFD, 60%, eighteen weeks) and angiotensin II (AngII) infusion (four weeks), we studied the effect of RvD2 administration in aorta and small mesenteric arteries structure and function and markers of inflammation. In human macrophages we evaluated the effects of AngII and RvD2 in macrophages function and SPMs profile. In patients, we found positive correlations between AAA and obesity, and between AAA and expression of ALOX15, RvD2 receptor GPR18, and pro-inflammatory genes. There was an inverse correlation between the expression of aortic ALOX15 and AAA growth rate. In the mice model, RvD2 partially prevented the HFD plus AngII-induced obesity and adipose tissue inflammation, hypertension, aortic and mesenteric arteries remodeling, hypercontratility and endothelial dysfunction, and the expression of vascular proinflammatory markers and cell apoptosis. In human macrophages, RvD2 prevented AngII-induced impaired efferocytosis and switched SPMs profile. RvD2 might represent a novel protective strategy in preventing vascular damage associated to hypertension and obesity likely through effects in vascular and immune cells.},
organization = {Funding: This work is supported by SAF2016-80305P, funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”, PID2020-116498RB-I00 to AMB and PID2021-122388OB-100 to JMR funded by MCIN/AEI/10.13039/501100011033, Comunidad de Madrid (CM) (B2017/BMD-3676 AORTASANA) FEDER-a way to build Europe, FIS PI21/00084 (Carlos III Health Institute) and INNVAL21/24 (IDIVAL) to FN, and the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement no. 954798 to AMB and European Research Council under the European Union’s Horizon 2020 research and innovation programme grant no: 677542 to JD. RRD was supported by a Juan de la Cierva contract (IJCI-2017-31399). There is no financial or personal relationship with organizations that could potentially influence the described research.
Acknowledgements: The authors thank Maria Encarnacion ´ Fern´ andez-Valle from the Bioimaging Center of the Universidad Complutense de Madrid, for her help with MRI experiments.},
publisher = {Editions Scientifiques Elsevier},
publisher = {Biomedicine & Pharmacotherapy, 2024, 174, 116564},
title = {Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors},
author = {Rodrigues-Diez, Raquel and Ballesteros-Martínez, Constanza and Moreno-Carriles, Rosa María and Nistal Herrera, Juan Francisco and Díaz del Campo, Lucía S. and Cachofeiro, Victoria and Dalli, Jesmond and García-Redondo, Ana B. and Redondo, Juan M. and Salaices, Mercedes and Briones, Ana M.},
}