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

Bone marrow transplantation improves endothelial function in hypertensive Dahl salt-sensitive rats.
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DOI:
10.1016/j.jash.2012.08.003
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发表时间:
2012-09
期刊:
Journal of the American Society of Hypertension : JASH
影响因子:
--
通讯作者:
Zhou MS
Zhou MS
中科院分区:
其他
文献类型:
--
作者:
Yu H;Shao H;Yan J;Tsoukias NM;Zhou MS

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骨髓来源的内皮祖细胞(EPCs)是维持内皮完整性和血管稳态的重要内源性系统。心血管危险因素与内皮祖细胞数量和功能能力降低有关。我们研究了将Dahl盐抗性大鼠骨髓来源细胞移植到年龄匹配的Dahl盐敏感大鼠体内对血压、内皮功能和循环EPC数的影响。BMT后分别饲喂正常(0.5% NaCl, NS)和高盐(4% NaCl, HS)饲料6周。以NS或HS饮食不含BMT的DS大鼠为对照。高血压DS (HS-DS)大鼠(收缩压:213±4 mmHg vs. NS组152±4 mmHg, p<0.05)表现为内皮依赖性乙酰胆碱(EDR)松弛受损,血管氧化应激和促炎细胞因子基因表达增加,eNOS表达降低。BMT可显著改善HS-DS大鼠的EDR和eNOS表达,降低氧化应激,但不降低收缩压(206±6 mmHg)。流式细胞术分析显示,高血压大鼠和正常大鼠循环EPCs的数量无差异,通过表达EPCs标志物CD34、cKit和血管内皮生长因子来证明。令人惊讶的是,BMT导致高血压大鼠上述EPC标记物增加5-10倍,而正常大鼠则没有。这些结果表明,DS大鼠在HS饮食挑战下增加骨髓源性EPCs的能力受损,这可能导致内皮功能障碍。
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 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 mmHg vs. 152 ± 4 mmHg in NS, p<0.05) 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 mmHg). 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 5–10 fold increase in the above-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.
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影响因子: --
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