Continuous infusion of resolvin D2 in combination with Angiotensin-II show contrary effects on blood pressure and intracardiac artery remodeling.

Autor: Olsen MB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway. Electronic address: maribol@medisin.uio.no., Louwe MC; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Yang K; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Øgaard J; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Dahl TB; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Gregersen I; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Alfsnes K; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Lauritzen KH; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway., Murphy SL; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Ahmed MS; Institute for Surgical Research, Oslo University Hospital, Oslo, Norway., Aukrust P; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway., Vinge LE; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Institute for Surgical Research, Oslo University Hospital, Oslo, Norway; Department of Medicine, Diakonhjemmet Hospital, Oslo, Norway., Yndestad A; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Holven KB; Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway., Halvorsen B; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway., Fosshaug LE; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Cardiology, Oslo University Hospital Ullevål, Oslo, Norway.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2024 Nov 12; Vol. 733, pp. 150706. Date of Electronic Publication: 2024 Sep 15.
DOI: 10.1016/j.bbrc.2024.150706
Abstrakt: Specialized pro-resolving mediators (SPMs) are key effectors of resolution of inflammation. This is highly relevant for cardiac and vessel remodeling, where the net inflammatory response contributes to determine disease outcome. Herein, we used a mice model of angiotensin (Ang)-II-induced hypertension to study the effect of the SPM Resolvin D2 (RvD2), on hypertension and cardiac remodeling. By using subcutaneous osmotic minipumps, mice were treated with PBS or Ang-II in combination with or without RvD2 for two weeks. Mice receiving RvD2 gained less blood pressure increase compared to Ang-II alone. Surprisingly, however, examination of intracardiac arteries revealed that RvD2 treatment in combination with Ang-II exacerbated Ang-II-induced fibrosis. Measures of vascular smooth muscle cell dedifferentiation correlated with the level of vascular remodeling, indicating that this dedifferentiation, including increased proliferation and migration, is a contributing factor. RNA sequencing of left ventricle cardiac tissue supported these findings as pathways related to cell proliferation and cell differentiation were upregulated in mice treated with Ang-II in combination with RvD2. Additionally, the RNA sequencing also showed upregulation of pathways related to SPM metabolism. In line with this, Mass spectrometry analysis of lipid mediators showed reduced cardiac levels of the arachidonic acid derived metabolite leukotriene E4 in RvD2 treated mice. Our study suggests that continuous infusion through osmotic minipumps should not be the recommended route of RvD2 administration in future studies.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Bente Halvorsen reports financial support was provided by South-Eastern Norway Regional Health Authority. Kirsten Holven reports financial support was provided by Throne-Holst Foundation for Nutrition Research. Maria Belland Olsen reports financial support was provided by Nansenfondet. Kirsten B Holven reports a relationship with Sanofi that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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