Impaired Endothelial Repair Capacity of Early Endothelial Progenitor Cells in Prehypertension: Relation to Endothelial Dysfunction

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 55; no. 6; pp. 1389 - 1397
• Main Authors: Giannotti, Giovanna, Doerries, Carola, Mocharla, Pavani S., Mueller, Maja F., Bahlmann, Ferdinand H., Horvàth, Tibor, Jiang, Hong, Sorrentino, Sajoscha A., Steenken, Nora, Manes, Costantina, Marzilli, Mario, Rudolph, K. Lenhard, Lüscher, Thomas F., Drexler, Helmut, Landmesser, Ulf
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.06.2010; Lippincott Williams & Wilkins
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Cardiology. Vascular system; Carotid Artery Injuries; Disease Models, Animal; Endothelial Cells - cytology; Endothelial Cells - physiology; Endothelium, Vascular - physiopathology; Fundamental and applied biological sciences. Psychology; Humans; Hypertension - blood; Hypertension - physiopathology; Medical sciences; Mice; Middle Aged; Neovascularization, Physiologic; Nitric Oxide - metabolism; Oxidative Stress; Probability; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Sampling Studies; Spectrometry, Fluorescence; Stem Cells - cytology; Stem Cells - physiology; Superoxides - metabolism; Vertebrates: cardiovascular system; Hypertension; endothelial function; NO; Endothelial cell; Senescence; early endothelial progenitor cells; prehypertension; Cardiovascular disease
• ISSN: 0194-911X; 1524-4563; 1524-4563
• DOI: 10.1161/HYPERTENSIONAHA.109.141614

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 area15±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.