Bone marrow transplantation improves endothelial function in hypertensive Dahl salt-sensitive rats - PubMed (original) (raw)

Bone marrow transplantation improves endothelial function in hypertensive Dahl salt-sensitive rats

Hong Yu et al. J Am Soc Hypertens. 2012 Sep-Oct.

Abstract

Bone marrow-derived endothelial progenitor cells (EPCs) constitute an important endogenous system in the maintenance of endothelial integrity and vascular homeostasis. Cardiovascular risk factors are associated with a reduced number and functional capacity of EPCs. Here we investigated the effect of transplantation of bone marrow-derived cells from Dahl salt-resistant rat into age-matched Dahl salt-sensitive (DS) rat on blood pressure, endothelial function, and circulating EPC number. The recipient DS rats were fed a normal (0.5% NaCl, NS) or high-salt (4% NaCl, HS) diet for 6 weeks after bone marrow transplantation (BMT). DS rats on a NS or a HS diet without BMT were used as controls. Hypertensive DS (HS-DS) rat (systolic blood pressure: 213 ± 4 mm Hg vs. 152 ± 4 mm Hg in NS, P < .05) manifested impaired endothelium-dependent relaxation to acetylcholine (EDR), increased gene expression of vascular oxidative stress and proinflamamtory cytokines, and decreased eNOS expression. BMT on HS-DS rat significantly improved EDR and eNOS expression, reduced oxidative stress without reduction in SBP (206 ± 6 mm Hg). Flow cytometry analysis showed that there was no difference in the number of circulating EPCs, demonstrated by expression of EPC markers CD34, cKit, and vascular endothelial growth factor, between hypertensive and normotensive rats. Surprisingly, BMT resulted in a 5- to 10-fold increase in the previously mentioned EPC markers in hypertensive, but not normotensive rat. These results suggest that DS rat has an impaired ability to increase bone marrow-derived EPCs in response to HS diet challenge, which may contribute to endothelial dysfunction.

Copyright © 2012 American Society of Hypertension. Published by Elsevier Inc. All rights reserved.

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Figures

Figure 1

Figure 1. Effects of bone marrow transplantation (BMT) on systolic blood pressure (SBP)in the recipient DS rats

High salt diet intake for 6 weeks significantly increased SBP in DS rats, compared with normotensive DS rats. BMT from DR rat into DS rat did not affect SBP in both normotensive (NS/BMT) and hypertensive (HS/BMT) DS rats. N=5–6. *P<0.05 vs. NS group, #p<0.05 vs. HS group.

Figure 2

Figure 2. Effects of BMT on body weight (BW, A), aortic weight (AW, B), and heart weight (HW/100 g BW, C) in the recipient DS rats

Hypertensive DS rats had a slight but significant inhibition in body weight gain compared with NS-DS rats. BMT from DR rat into DS rat further inhibited body weight gain in both normotensive (NS/BMT) and hypertensive (HS/BMT) DS rats. Hypertensive DS rats manifested an increase in AW (aortic hypertrophy) and HW (cardiac hypertrophy) compared with normotensive DS rats, BMT did not affect AW and HW in both normotensive and hypertensive DS rats. N=5–6, *P<0.05 vs. NS group, #p<0.05 vs. HS group.

Figure 3

Figure 3. The circulating endothelial progenitor cell (EPC) number in DR and recipient DS rats

EPCs were characterized by flow cytometry using double markers: CD34+/cKit+ (A), CD34+/VEGFR2+(B), cKit+/VEGFR2+ (C). There is no significant difference in EPCs markers including CD34+/cKit+, CD34+/VEGFR2+, or cKit+/VEGFR2+ among DR, normotensive or hypertensive DS rats. BMT from DR rats into DS rats significantly increased all EPCs markers in hypertensive DS rats (HS/BMT) but not in normotensive DS rats (NS/BMT). N=4–5. *P<0.05. ND: no significant difference.

Figure 4

Figure 4. Effects of BMT on endothelium-dependent relaxation (EDR) in the recipient DS rats

EDR to acetylcholine was significantly reduced in hypertensive DS rats, compared with normotensive DS rats. BMT from DR rats into DS rats significantly improved EDR in hypertensive DS rats but did not affect EDR in normotensive DS rats. N=5–6, *P<0.05.

Figure 5

Figure 5. Effects of BMT on aortic gene expression in the recipient DS rats

Hypertensive DS rats had a significant increase in mRNA expression of gp91phox (A), p22phox (B) compared with normotensive DS rats', BMT significantly reduced mRNA expression of gp91phox and p22 phox in hypertensive but not in normotensive DS rats. Hypertensive DS rats exhibited a reduction in eNOS (C) expression and an increase in the expression of proinflammatory cytokine TNFa (D) and MCP1 (E), BMT normalized eNOS expression but not inflammatory cytokines in hypertensive DS rats. N=4, *P<0.05 vs. NS group, #p<0.05 vs. HS group.

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References

    1. Schulman IH, Zhou MS, Raij L. Interaction between nitric oxide and angiotensin II in the endothelium: role in atherosclerosis and hypertension. J Hypertens. 2006;24:S45–50. - PubMed
    1. Hill JM, Zalos G, Halcox JP, Schenke WH, Waclawiw MA, Quyyumi AA, Finkel T. Circulating endothelial progenitor cells, vascular function, and cardiovascular risk. N Engl J Med. 2003;348:593–600. - PubMed
    1. Zhou MS, Hernandez Schulman I, Pagano PJ, Jaimes EA, Raij L. Reduced NAD(P)H oxidase in low renin hypertension: link among angiotensin II, atherogenesis, and blood pressure. Hypertension. 2006;47:81–6. - PubMed
    1. Werner N, Koriol S, Schiegl T, Ahlers P, Walenta K, Link A, Bohm M, Nickenig G. Circulating endothelial progenitor cells and cardiovascular outcomes. N Engl J Med. 2005;353:999–1007. - PubMed
    1. Schmidt-Lucke C, Rossig L, Fichtlscherer S, Vasa M, Britten M, Kamper U, Dimmeler S, Zeiher AM. Reduced number of circulating endothelial progenitor cells predicts future cardiovascular events: proof of concept for the clinical importance of endogenous vascular repair. Circulation. 2005;111:2981–7. - PubMed

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