Resolvin D2 prevents vascular remodeling, hypercontractility and endothelial dysfunction in obese hypertensive mice through modulation of vascular and proinflammatory factors
Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:174 |
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| Enthalten in: |
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie - 174(2024) vom: 10. Mai, Seite 116564 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rodrigues-Diez, Raquel [VerfasserIn] |
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| Links: |
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| Themen: |
11128-99-7 |
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| Anmerkungen: |
Date Completed 30.04.2024 Date Revised 30.04.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.biopha.2024.116564 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 520 | |a Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Endothelial dysfunction | |
| 650 | 4 | |a Hypertension | |
| 650 | 4 | |a Obesity | |
| 650 | 4 | |a Resolution of inflammation | |
| 650 | 4 | |a Resolvin D2 | |
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| 700 | 1 | |a Ballesteros-Martinez, Constanza |e verfasserin |4 aut | |
| 700 | 1 | |a Moreno-Carriles, Rosa María |e verfasserin |4 aut | |
| 700 | 1 | |a Nistal, Francisco |e verfasserin |4 aut | |
| 700 | 1 | |a Díaz Del Campo, Lucía S |e verfasserin |4 aut | |
| 700 | 1 | |a Cachofeiro, Victoria |e verfasserin |4 aut | |
| 700 | 1 | |a Dalli, Jesmond |e verfasserin |4 aut | |
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| 700 | 1 | |a Salaices, Mercedes |e verfasserin |4 aut | |
| 700 | 1 | |a Briones, Ana M |e verfasserin |4 aut | |
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