MITOVASC Laboratory, UMR CNRS 6015, INSERM U1083, Angers University, Angers, France.
Cardiovascular Functions In Vitro (CARFI) Facility, Angers University, Angers, France.
J Vasc Res. 2021;58(1):16-26. doi: 10.1159/000511799. Epub 2020 Dec 2.
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.
血流介导的外向重塑（FMR）参与缺血后再血管化。血管紧张素 II 型受体（AT2R）通过激活 T 细胞介导的白介素 17 产生，以及雌激素参与 FMR。因此，我们使用体内小鼠肠系膜动脉供血动脉结扎模型研究了雌激素和 AT2R 在 FMR 中的相互作用。在 2 天（炎症期）、4 天（直径扩张期）和 7 天（重塑完成）后收集动脉。我们使用 AT2R+/+和 AT2R-/-去卵巢（OVX）雌性小鼠，并用 17-β-雌二醇（E2）处理或不处理。结扎后 7 天，高血流（HF）动脉的直径大于正常血流（NF）动脉。OVX 小鼠中不存在 FMR，并且 E2 可恢复 FMR。仅在 E2 处理的 OVX AT2R+/+小鼠中，HF 动脉中的 AT2R 基因表达高于 NF 动脉。仅在 E2 处理的 AT2R+/+小鼠中，CD11b 和 TNF alpha 水平（炎症期）、MMP2 和 TIMP1（细胞外基质消化）以及 NOS3（直径扩张期）表达水平高于 NF 动脉，而在其他组中则没有。因此，E2 是 AT2R 依赖性直径扩张所必需的，可能通过激活 T 细胞 AT2R，在长期处于高血流的动脉中。
