Yu Hong, Shao Hongwei, Yan Jing, Tsoukias Nikolaos M, Zhou Ming-Sheng
Department of Cardiology, 2nd Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
J Am Soc Hypertens. 2012 Sep-Oct;6(5):331-7. doi: 10.1016/j.jash.2012.08.003.
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.
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EPCs数量减少和功能能力下降有关。在此，我们研究了将 Dahl 盐抵抗大鼠的骨髓来源细胞移植到年龄匹配的 Dahl 盐敏感（DS）大鼠体内对血压、内皮功能和循环EPCs数量的影响。骨髓移植（BMT）后，受体DS大鼠接受正常（0.5% NaCl，NS）或高盐（4% NaCl，HS）饮食6周。未进行BMT的NS或HS饮食的DS大鼠用作对照。高血压DS（HS-DS）大鼠（收缩压：213±4 mmHg，而NS组为152±4 mmHg，P<0.05）表现出对乙酰胆碱的内皮依赖性舒张功能受损（EDR）、血管氧化应激和促炎细胞因子的基因表达增加以及eNOS表达降低。HS-DS大鼠进行BMT可显著改善EDR和eNOS表达，降低氧化应激但收缩压未降低（206±6 mmHg）。流式细胞术分析显示，高血压大鼠和正常血压大鼠之间，通过EPC标志物CD34、cKit和血管内皮生长因子的表达所证明的循环EPCs数量没有差异。令人惊讶的是，BMT导致高血压大鼠而非正常血压大鼠中上述EPC标志物增加5至10倍。这些结果表明，DS大鼠对HS饮食挑战增加骨髓来源EPCs的能力受损，这可能导致内皮功能障碍。
