title: Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction.
abstract: 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.
authors.affiliation: Department of Cardiology, Cardiovascular Center, University Hospital Zürich, Zürich, Switzerland.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Giannotti
authors.forename: Carola
authors.initials: C
authors.lastname: Doerries
authors.forename: Pavani S
authors.initials: PS
authors.lastname: Mocharla
authors.forename: Maja F
authors.initials: MF
authors.lastname: Mueller
authors.forename: Ferdinand H
authors.initials: FH
authors.lastname: Bahlmann
authors.forename: Tibor
authors.initials: T
authors.lastname: Horvàth
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
authors.forename: Sajoscha A
authors.initials: SA
authors.lastname: Sorrentino
authors.forename: Nora
authors.initials: N
authors.lastname: Steenken
authors.forename: Costantina
authors.initials: C
authors.lastname: Manes
authors.forename: Mario
authors.initials: M
authors.lastname: Marzilli
authors.forename: K Lenhard
authors.initials: KL
authors.lastname: Rudolph
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lüscher
authors.forename: Helmut
authors.initials: H
authors.lastname: Drexler
authors.forename: Ulf
authors.initials: U
authors.lastname: Landmesser
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000166:cytology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000503:physiopathology*; D051379:Mice; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D009569:Nitric Oxide / Q000378:metabolism; D018384:Oxidative Stress; D011336:Probability; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012494:Sampling Studies; D013050:Spectrometry, Fluorescence; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism
chemical_list: D013481:Superoxides; D009569:Nitric Oxide