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SNS driven hypertension enhances hematopoiesis
mobilization of HSPCs by acting on key niche cells along with stimulating neutrophils to secrete proteases that cleave the retention receptor CXCR4 on HSPCs.
Suppressing chronic sympathetic signaling dampens myelopoiesis in hypertensive Apoe–/– mice
Having observed a restoration in the HSPC BM microenvironment when BPH/Apoe-/- mice were treated with propranolol, we explored if this was also reflected by normalization of myelopoiesis in these mice. Following
treatment with propranolol, we observed a reduction in circulating monocytes and neutrophils (Figure 5A). We determined if this reduction was echoed by changes in the BM stem and progenitor populations. Following adminis- tration of propranolol, the abundance of BM HSPCs was not affected; however, these cells were proliferating at lower rates and giving rise to fewer GMPs (Figure 5, B-D). Consistent with an improvement in the HSPC microenvi- ronment, there were fewer mobilized HSPCs and MPCs
F
G
in the blood of the BPH/Apoe-/- ABC
mice treated with propra-
DE
H
Figure 5. Propranolol prevents extramedullary hematopoiesis in BPH/Apoe-/- mice. BPH/Apoe- /- mice were fed a WTD for 16 weeks and treated with vehicle or Propranolol (0.5 g/L) in drinking water. Flow cytometry was used to assess A) circulat- ing monocytes(M)/neu- trophils(N), B) BM HSPCs and C) proportion of which are pro- liferating along with D) of BM GMPs. E) Blood HSPC and MPC populations. F) Spleen HSPC and G) GMP populations along with H) proliferating splenic HSPCs and GMPs were assessed by flow cytometry. I) Splenic monocyte(M)/neu- trophil(N) populations. Data are presented as mean ± SEM where *P<0.05, **P<0.01 and ***P<0.001 (Student’s t-test). A-I) n= 6-10.
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