Reduced number of circulating endothelial progenitors and HOXA9 expression in CD34+cells of hypertensive patients
Reduced number of circulating endothelial progenitors and HOXA9 expression in CD34+cells of hypertensive patients
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DOI：
10.1097/hjh.0b013e32828e506d
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发表时间：
2007-10-01
影响因子：
4.9
通讯作者：
Mannarino, Elmo
中科院分区：
文献类型：
--
作者：
Pirro, Matteo;Schillaci, Giuseppe;Mannarino, Elmo
目的循环内皮祖细胞（EPCs）分化为成熟内皮细胞，使损伤的内皮细胞再生。同源盒 A9 (HOXA9) 在祖细胞成熟、产后新生血管形成和血管修复过程中对于内皮定型至关重要。本研究的目的是测定高血压患者 CD34R 细胞中 HOXA9 的表达，并探讨其与循环 EPC 数量的相关性。 方法 招募 30 名新诊断、从未治疗过的原发性高血压患者和 30 名年龄和性别匹配的正常血压对照者参与本研究。从外周 CD34+ 细胞中提取总 RNA，并进行定量实时聚合酶链反应以测量 HOXA9 表达。测量CD34+/人激酶插入结构域蛋白受体R（KDR+）EPCs的数量并估计Framingham风险。结果与正常血压受试者相比，高血压患者HOXA9表达降低（-26%，P<0.001），并且外周CD34+/KDR+EPCs水平较低（421+/-93 vs 582+/-101，P<0.001）。 HOXA9表达与收缩压呈负相关（rUS0.54，P<0.001），Framingham风险=0.50，P<0.001）。 EPC 数量与 HOXA9 表达之间存在直接关联（r=0.50，P<0.001），且与血压水平和 Framingham 风险无关。在由 15 名高血压患者组成的亚组中，雷米普利 4 周治疗与 HOXA9 表达显着增加 15% 和 EPC 水平显着增加 25% 相关。结论在高血压患者中，外周 CD34R 细胞中 HOXA9 表达的下调可能在循环 EPC 损失中发挥作用，从而可能损害出生后新生血管形成和血管修复。
Objective Circulating endothelial progenitor cells ( EPCs) differentiate into mature endothelial cells and regenerate the injured endothelium. The role of homeobox A9 ( HOXA9) is critical for endothelial commitment during progenitor cell maturation, postnatal neovascularization and vascular repair. The objective of our study was to measure the expression of HOXA9 in CD34R cells from hypertensive patients and to investigate its correlation with the number of circulating EPCs.Methods Thirty patients with newly diagnosed, never-treated essential hypertension and 30 age- and sexmatched normotensive controls were recruited for the study. Total RNA was extracted from peripheral CD34+cells and quantitative real- time polymerase chain reaction for measurement of HOXA9 expression was performed. The number of CD34+/ human kinase insert domain protein receptor R ( KDR+) EPCs was measured and the Framingham risk estimated.Results Hypertensive patients had reduced HOXA9 expression compared to normotensive subjects ( -26%, P< 0.001), and lower levels of peripheral CD34+/ KDR+ EPCs ( 421 +/- 93 versus 582 +/- 101, P< 0.001). HOXA9 expression was inversely associated with systolic blood pressure ( rUS0.54, P< 0.001) and the Framingham riskr=0.50, P< 0.001). A direct association was observed between the number of EPCs and HOXA9 expression ( r=0.50, P< 0.001), which was independent of blood pressure levels and Framingham risk. In a subgroup of 15 hypertensive patients, a 4- week treatment with ramipril was associated with a significant 15% increase in HOXA9 expression and 25% increase in EPC levels.Conclusions In hypertensive patients, downregulation of HOXA9 expression in peripheral CD34R cells may have a role in the loss of circulating EPCs, thus potentially impairing postnatal neovascularization and vascular repair.