Reversal of aging-associated increase in myelopoiesis and expression of alarmins by angiotensin-(1-7).
Reversal of aging-associated increase in myelopoiesis and expression of alarmins by angiotensin-(1-7).
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DOI：
10.1038/s41598-023-29853-w
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发表时间：
2023-02-13
影响因子：
4.6
通讯作者：
Jarajapu, Yagna P. R.
中科院分区：
文献类型：
--
作者：
Chittimalli, Kishore;Jahan, Jesmin;Sakamuri, Anil;Weyrick, Hope;Winkle, Wink;Adkins, Steven;Vetter, Stefan W.;Jarajapu, Yagna P. R.
衰老与慢性全身性炎症有关，主要是由于骨髓生成增加，这反过来又增加了血管疾病的风险。我们先前已经显示了血管紧张素-（1-7）（Ang-（1-7））在逆转衰老中的血管修复功能障碍方面的治疗潜力的证据。本研究验证了Ang-（1-7）在衰老中的缺血性血管修复涉及骨髓中骨髓生成潜能的衰减和炎性细胞动员的减少的假设。3-4月龄和22-24月龄的年轻或老年雄性小鼠分别接受Ang-（1-7）（1 μg/kg/min，s.c.）四周。通过进行殖民地（CFU-GM）测定，然后进行单核细胞-巨噬细胞流式细胞术，在骨髓（BM）细胞中评价骨髓生成。评价造血祖细胞富集的BM细胞中促骨髓生成因子和alarmin的表达。通过股动脉结扎诱导后肢缺血（HLI），并测定单核细胞向血流中的动员。通过激光多普勒成像监测血流恢复，并通过免疫组织化学评价炎性细胞浸润。与年轻小鼠相比，来自老年小鼠的BM细胞产生更多数量的单核细胞（Ly 6 G-CD 11b + Ly 6Chi）和M1巨噬细胞（Ly 6ChiF 4/80+），这被Ang-（1-7）逆转。与年轻骨髓细胞相比，在老年造血祖细胞富集的BM细胞中，选定的骨髓生成因子alarmin（S100 A8、S100 A9、S100 A14和HMGb 1）和alarmin受体Alarmin的基因表达更高。Ang-（1-7）可抑制这些因子的表达。与年轻小鼠相比，老年小鼠中缺血诱导的单核细胞动员更高，血流恢复减少，单核细胞-巨噬细胞浸润增加，所有这些都被Ang-（1-7）逆转。Ang-（1-7）在衰老过程中增强缺血性血管修复主要是通过减少炎症性单核细胞-巨噬细胞向缺血性损伤区域的产生和募集。这与BM-造血祖细胞中alarmin信号传导减少有关。
Aging is associated with chronic systemic inflammation largely due to increased myelopoiesis, which in turn increases risk for vascular disease. We have previously shown evidence for the therapeutic potential of Angiotensin-(1–7) (Ang-(1–7)) in reversing vasoreparative dysfunction in aging. This study tested the hypothesis that ischemic vascular repair in aging by Ang-(1–7) involves attenuation of myelopoietic potential in the bone marrow and decreased mobilization of inflammatory cells. Young or Old male mice of age 3–4 and 22–24 months, respectively, received Ang-(1–7) (1 µg/kg/min, s.c.) for four weeks. Myelopoiesis was evaluated in the bone marrow (BM) cells by carrying out the colony forming unit (CFU-GM) assay followed by flow cytometry of monocyte-macrophages. Expression of pro-myelopoietic factors and alarmins in the hematopoietic progenitor-enriched BM cells was evaluated. Hindlimb ischemia (HLI) was induced by femoral ligation, and mobilization of monocytes into the blood stream was determined. Blood flow recovery was monitored by Laser Doppler imaging and infiltration of inflammatory cells was evaluated by immunohistochemistry. BM cells from Old mice generated a higher number of monocytes (Ly6G-CD11b+Ly6Chi) and M1 macrophages (Ly6ChiF4/80+) compared to that of Young, which was reversed by Ang-(1–7). Gene expression of selected myelopoietic factors, alarmins (S100A8, S100A9, S100A14 and HMGb1) and the receptor for alarmins, RAGE, was higher in the Old hematopoietic progenitor-enriched BM cells compared to the Young. Increased expressions of these factors were decreased by Ang-(1–7). Ischemia-induced mobilization of monocytes was higher in Old mice with decreased blood flow recovery and increased infiltration of monocyte-macrophages compared to the Young, all of which were reversed by Ang-(1–7). Enhanced ischemic vascular repair by Ang-(1–7) in aging is largely by decreasing the generation and recruitment of inflammatory monocyte-macrophages to the areas of ischemic injury. This is associated with decreased alarmin signaling in the BM-hematopoietic progenitor cells.
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影响因子：
4.6
作者：
Danilov SM;Lünsdorf H;Akinbi HT;Nesterovitch AB;Epshtein Y;Letsiou E;Kryukova OV;Piegeler T;Golukhova EZ;Schwartz DE;Dull RO;Minshall RD;Kost OA;Garcia JG
通讯作者：
Garcia JG
影响因子：
9.3
作者：
Ehlermann, Philipp;Eggers, Kai;Remppis, Andrew
通讯作者：
Remppis, Andrew
DOI：
10.1152/ajpheart.00393.2007
发表时间：
2007-09-01
影响因子：
4.8
作者：
Basso, Nidia;Cini, Rosa;Inserra, Felipe
通讯作者：
Inserra, Felipe
影响因子：
8
作者：
Adamopoulos, Christos;Piperi, Christina;Papavassiliou, Athanasios G.
通讯作者：
Papavassiliou, Athanasios G.
DOI：
10.1002/path.5330
发表时间：
2019-12
期刊：
The Journal of pathology
影响因子：
--
作者：
Barman PK;Urao N;Koh TJ
通讯作者：
Koh TJ