Aging is associated with impaired vascular repair following ischemic insult, largely due to reparative dysfunctions of progenitor cells. Activation of Mas receptor (MasR) was shown to reverse aging-associated vasoreparative dysfunction. This study tested the impact of MasR-deficiency on mobilization and vasoreparative functions with aging. Wild type (WT) or MasR-deficient mice (MasR^−/− or MasR^+/−) at 12–14 weeks (young) or middle age (11–12 months) (MA) were used in the study. Mobilization of lineage-negative, Sca-1-positive cKit-positive (LSK) cells in response to G-CSF or plerixafor was determined. Hindlimb ischemia (HLI) was induced by femoral artery ligation. Mobilization and blood flow recovery were monitored post-HLI. Radiation chimeras were made by lethal irradiation of WT or MasR^−/− mice followed by administration of bone marrow cells from MasR^−/− or WT mice, respectively. Nitric oxide (NO) generation by stromal-derived factor-1α (SDF) and mitochondrial reactive oxygen species (mitoROS) levels were determined by flow cytometry. Effect of A779 treatment on mobilization, blood flow recovery, and NO and ROS levels were determined in young WT and MasR^+/− mice. Circulating LSK cells in basal or in response to plerixafor or G-CSF or in response to ischemic injury were lower in MasR^−/− mice compared to the WT. Responses in MasR^+/− mice were similar to the WT at young age but at the middle age, impairments were observed. Impaired mobilization to ischemia or G-CSF was rescued in WT → MasR^−/− chimeras. NO levels were lower and mitoROS were higher in MasR^−/− LSK cells compared to WT cells. A779 precipitated dysfunctions in young-MasR^+/− mice similar to that observed in MA-MasR^+/−, and this accompanied decreased NO generation by SDF and enhanced mitoROS levels. This study shows that mice at MA do not exhibit vasoreparative dysfunction. Either partial or total loss of MasR precipitates advanced-aging phenotype likely due to lack of NO and oxidative stress.

衰老与缺血性损伤后血管修复受损有关，主要是由于祖细胞的修复功能障碍。Mas 受体 (MasR) 的激活被证明可以逆转衰老相关的血管修复功能障碍。这项研究测试了 MasR 缺乏对随着年龄的增长而动员和血管修复功能的影响。野生型 (WT) 或 MasR 缺陷型小鼠（MasR ^-/-或 MasR ^+/-）在研究中使用 12-14 周（年轻）或中年（11-12 个月）（MA）。确定了响应 G-CSF 或普乐沙福的谱系阴性、Sca-1 阳性 cKit 阳性 (LSK) 细胞的动员。股动脉结扎诱导后肢缺血（HLI）。在 HLI 后监测动员和血流恢复。辐射嵌合体是通过对 WT 或 MasR ^{-/-小鼠进行致死辐射，然后分别给予来自 MasR -/-}或 WT 小鼠的骨髓细胞来制备的。通过流式细胞术测定基质衍生因子-1α (SDF) 产生的一氧化氮 (NO) 和线粒体活性氧 (mitoROS) 水平。在年轻 WT 和 MasR 中测定 A779 治疗对动员、血流恢复以及 NO 和 ROS 水平的影响^+/-老鼠。与 WT 相比，MasR ^-/-小鼠的基础循环 LSK 细胞或响应普乐沙福或 G-CSF 或响应缺血性损伤的循环 LSK 细胞较低。MasR ^+/-小鼠的反应在年轻时与 WT 相似，但在中年时，观察到损伤。在 WT → MasR ^-/-嵌合体中挽救了对缺血或 G-CSF 的动员受损。与 WT 细胞相比，MasR ^-/- LSK 细胞中的 NO 水平较低，mitoROS 较高。A779 在年轻-MasR ^+/-小鼠中引发功能障碍，类似于在 MA-MasR ^{+/-中观察到的功能障碍}，这伴随着 SDF 产生的 NO 减少和 mitoROS 水平的提高。这项研究表明，MA 小鼠没有表现出血管修复功能障碍。由于缺乏 NO 和氧化应激，MasR 的部分或全部丧失会导致晚期老化表型。