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Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction


Giannotti, G; Doerries, C; Mocharla, P S; Mueller, M F; Bahlmann, F H; Horvàth, T; Jiang, H; Sorrentino, S A; Steenken, N; Manes, C; Marzilli, M; Rudolph, K L; Lüscher, T F; Drexler, H; Landmesser, U (2010). Impaired endothelial repair capacity of early endothelial progenitor cells in prehypertension: relation to endothelial dysfunction. Hypertension, 55(6):1389-1397.

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.

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.

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Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology

04 Faculty of Medicine > University Hospital Zurich > Clinic for Cardiology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2010
Deposited On:19 Jan 2011 15:25
Last Modified:07 Dec 2017 06:01
Publisher:American Heart Association
ISSN:0194-911X
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1161/HYPERTENSIONAHA.109.141614
PubMed ID:20458006

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