Department of Cardiology, Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland.
Hypertension. 2010 Jun;55(6):1389-97. doi: 10.1161/HYPERTENSIONAHA.109.141614. Epub 2010 May 10.
Prehypertension is a highly frequent condition associated with an increased cardiovascular risk. Endothelial dysfunction is thought to promote the development of hypertension and vascular disease; however, underlying mechanisms remain to be further determined. The present study characterizes for the first time the in vivo endothelial repair capacity of early endothelial progenitor cells (EPCs) in patients with prehypertension/hypertension and examines its relation with endothelial function. Early EPCs were isolated from healthy subjects and newly diagnosed prehypertensive and hypertensive patients (n=52). In vivo endothelial repair capacity of EPCs was examined by transplantation into a nude mouse carotid injury model. EPC senescence was determined (RT-PCR of telomere length). NO and superoxide production of EPCs were measured using electron spin resonance spectroscopy analysis. CD34(+)/KDR(+) mononuclear cells and circulating endothelial microparticles were examined by fluorescence-activated cell sorter analysis. Endothelium-dependent and -independent vasodilations were determined by high-resolution ultrasound. In vivo endothelial repair capacity of EPCs was substantially impaired in prehypertensive/hypertensive patients as compared with healthy subjects (re-endothelialized area: 15+/-3%/13+/-2% versus 28+/-3%; P<0.05 versus healthy subjects). Senescence of EPCs in prehypertension/hypertension was substantially increased, and NO production was markedly reduced. Moreover, reduced endothelial repair capacity of early EPCs was significantly related to an accelerated senescence of early EPCs and impaired endothelial function. The present study demonstrates for the first time that in vivo endothelial repair capacity of early EPCs is reduced in patients with prehypertension and hypertension, is related to EPC senescence and impaired endothelial function, and likely represents an early event in the development of hypertension.
高血压前期是一种与心血管风险增加高度相关的常见病症。内皮功能障碍被认为可促进高血压和血管疾病的发展，但潜在机制仍有待进一步确定。本研究首次描述了高血压前期/高血压患者体内早期内皮祖细胞（EPC）的内皮修复能力，并研究了其与内皮功能的关系。从健康受试者和新诊断的高血压前期和高血压患者中分离出早期 EPC（n=52）。通过将 EPC 移植到裸鼠颈动脉损伤模型中来检测 EPC 的体内内皮修复能力。通过端粒长度的 RT-PCR 来测定 EPC 衰老。通过电子自旋共振光谱分析来测量 EPC 的 NO 和超氧化物产生。通过荧光激活细胞分选分析来检测 CD34(+)/KDR(+)单核细胞和循环内皮微颗粒。通过高分辨率超声来测定内皮依赖性和非依赖性血管舒张功能。与健康受试者相比，高血压前期/高血压患者体内 EPC 的内皮修复能力明显受损（再内皮化面积：15+/-3%/13+/-2%与 28+/-3%；P<0.05 与健康受试者相比）。高血压前期/高血压患者的 EPC 衰老明显增加，NO 产生明显减少。此外，早期 EPC 内皮修复能力的降低与早期 EPC 衰老加速和内皮功能受损显著相关。本研究首次证明，高血压前期和高血压患者体内早期 EPC 的内皮修复能力降低，与 EPC 衰老和内皮功能受损有关，可能代表高血压发展的早期事件。
