1. Estrogens and the Angiotensin II Type 2 Receptor Control Flow-Mediated Outward Remodeling in the Female Mouse Mesenteric Artery
- Author
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Laurent Loufrani, Jordan Rivron, Emilie Vessieres, Daniel Henrion, Jean-François Arnal, Anne-Laure Guihot, Linda Grimaud, Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and INSERM U1048 (I2CM)
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Nitric Oxide Synthase Type III ,Physiology ,Ovariectomy ,Vascular Remodeling ,030204 cardiovascular system & hematology ,Mechanotransduction, Cellular ,Receptor, Angiotensin, Type 2 ,03 medical and health sciences ,0302 clinical medicine ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,In vivo ,Internal medicine ,medicine ,Animals ,Mesenteric arteries ,ComputingMilieux_MISCELLANEOUS ,TIMP1 ,Mice, Knockout ,CD11b Antigen ,Tissue Inhibitor of Metalloproteinase-1 ,Estradiol ,Tumor Necrosis Factor-alpha ,Chemistry ,Estrogen Replacement Therapy ,Blood flow ,Mesenteric Arteries ,Mice, Inbred C57BL ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Regional Blood Flow ,Ovariectomized rat ,Matrix Metalloproteinase 2 ,Female ,Tumor necrosis factor alpha ,Stress, Mechanical ,Cardiology and Cardiovascular Medicine ,Ligation ,Artery - Abstract
Flow-mediated outward remodeling (FMR) is involved in postischemic revascularization. Angiotensin II type 2 receptor (AT2R), through activation of T-cell-mediated IL-17 production, and estrogens are involved in FMR. Thus, we investigated the interplay between estrogens and AT2R in FMR using a model of ligation of feed arteries supplying collateral pathways in mouse mesenteric arteries in vivo. Arteries were collected after 2 (inflammatory phase), 4 (diameter expansion phase), and 7 days (remodeling completed). We used AT2R+/+ and AT2R−/− ovariectomized (OVX) female mice treated or not with 17-beta-estradiol (E2). Seven days after ligation, arterial diameter was larger in high flow (HF) compared to normal flow (NF) arteries. FMR was absent in OVX mice and restored by E2. AT2R gene expression was higher in HF than in NF arteries only in E2-treated OVX AT2R+/+ mice. CD11b and TNF alpha levels (inflammatory phase), MMP2 and TIMP1 (extracellular matrix digestion), and NOS3 (diameter expansion phase) expression levels were higher in HF than in NF arteries only in E2-treated AT2R+/+ mice, not in the other groups. Thus, E2 is necessary for AT2R-dependent diameter expansion, possibly through activation of T-cell AT2R, in arteries submitted chronically to high blood flow.
- Published
- 2020