中国动脉硬化杂志2018,Vol.26Issue(3):265-272,8.
GTP环化水解酶Ⅰ/四氢生物蝶呤通路对高血压内皮祖细胞体外活性和体内再内皮化能力的调节
GTP cyclohydrolase Ⅰ/tetrahydrobiopterin pathway regulated the in-vitro function and in-vivo reendothelialization capacity of endothelial progenitor cells from hypertensive patients
摘要
Abstract
Aim To observe the regulation of GTP cyclohydrolase Ⅰ (GTPCH Ⅰ)/tetrahydrobiopterin (BH4) pathway on function of endothelial progenitor cells in hypertensive patients.Methods Nineteen hypertensive patients and nineteen healthy volunteers were observed.Endothelial progenitor cells were isolated from peripheral blood,cultured and identified.The in-vitro migration,proliferation,adhesion activity and in-vivo reendothelialization function of endothelial progenitor cells were detected.The model of arterial injury in nude mice was established and endothelial progenitor cells from hypertensive patients and healthy volunteers were transplanted to evaluate the reendothelialization capacity of endothelial progenitor cells.In addition,the mRNA expression of GTPCH Ⅰ/BH4,and the expression of nitric oxide (NO),cyclic guanosine monophosphate,and thrombospondin-1 (TSP-1) mRNA levels of endothelial progenitor cells were measured.Furthermore,RNA interfection,gene transfection and drug inhibition of GTPCH Ⅰ/BH4 were carried out to demonstrate its role in the regulation of endothelial progenitor cell function.Results The in-vitro migration,proliferation,adhesion activity and in-vivo reendothelialization function of endothelial progenitor cells were significantly decreased in hypertensive patients.In parallel,the expression of GTPCH Ⅰ/BH4,NO and cyclic guanosine monophosphate of endothelial progenitor cells were reduced,while the TSP-1 mRNA level was elevated.When blocking the GTPCH Ⅰ/BH4 pathway,the in-vitro migration,proliferation,adhesion activity and in-vivo reendothelialization function of endothelial progenitor cells from hypertensive patient and healthy volunteers were both weakened.Conclusion This study revealed that GTPCH Ⅰ/ BH4 pathway regulates the in-vitro and in-vivo function of endothelial progenitor cells from hypertensive patients,via regulation of TSP-1 and soluble guanylyl cyclases/cyclic guanosine monophosphate system.关键词
高血压/内皮祖细胞/再内皮化/GTP环化水解酶Ⅰ/四氢生物蝶呤Key words
Hypertension/Endothelial progenitor cells/Reendothelialization/GTP cyclohydrolase Ⅰ/Tetrahydrobiopterin分类
医药卫生引用本文复制引用
姚顺,吴少虹,柏勇平,曾海涛,李翔,彭智华,杨震..GTP环化水解酶Ⅰ/四氢生物蝶呤通路对高血压内皮祖细胞体外活性和体内再内皮化能力的调节[J].中国动脉硬化杂志,2018,26(3):265-272,8.基金项目
国家自然科学基金项目(81670220、31270992和30800215) (81670220、31270992和30800215)
广东省自然科学基金项目(2014A030313086) (2014A030313086)
广东省省级科技计划项目(2015A020212013和2013B021800275) (2015A020212013和2013B021800275)
中山大学青年教师培育项目(17ykzd18和13ykpy24) (17ykzd18和13ykpy24)
广州市科技计划珠江新星项目(2013J2200019) (2013J2200019)