Document Detail


Reduced number of circulating endothelial progenitors and HOXA9 expression in CD34+ cells of hypertensive patients.
MedLine Citation:
PMID:  17885552     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Circulating endothelial progenitor cells (EPCs) differentiate into mature endothelial cells and regenerate the injured endothelium. The role of homeobox A9 (HOXA9) is critical for endothelial commitment during progenitor cell maturation, postnatal neovascularization and vascular repair. The objective of our study was to measure the expression of HOXA9 in CD34+ cells from hypertensive patients and to investigate its correlation with the number of circulating EPCs. METHODS: Thirty patients with newly diagnosed, never-treated essential hypertension and 30 age- and sex-matched normotensive controls were recruited for the study. Total RNA was extracted from peripheral CD34+ cells and quantitative real-time polymerase chain reaction for measurement of HOXA9 expression was performed. The number of CD34+/human kinase insert domain protein receptor + (KDR+) EPCs was measured and the Framingham risk estimated. RESULTS: Hypertensive patients had reduced HOXA9 expression compared to normotensive subjects (-26%, P < 0.001), and lower levels of peripheral CD34+/KDR+ EPCs (421 +/- 93 versus 582 +/- 101, P < 0.001). HOXA9 expression was inversely associated with systolic blood pressure (r = -0.54, P < 0.001) and the Framingham risk (r = -0.50, P < 0.001). A direct association was observed between the number of EPCs and HOXA9 expression (r = 0.50, P < 0.001), which was independent of blood pressure levels and Framingham risk. In a subgroup of 15 hypertensive patients, a 4-week treatment with ramipril was associated with a significant 15% increase in HOXA9 expression and 25% increase in EPC levels. CONCLUSIONS: In hypertensive patients, downregulation of HOXA9 expression in peripheral CD34+ cells may have a role in the loss of circulating EPCs, thus potentially impairing postnatal neovascularization and vascular repair.
Authors:
Matteo Pirro; Giuseppe Schillaci; Cinzia Menecali; Francesco Bagaglia; Rita Paltriccia; Gaetano Vaudo; Massimo R Mannarino; Elmo Mannarino
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of hypertension     Volume:  25     ISSN:  0263-6352     ISO Abbreviation:  J. Hypertens.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-09-21     Completed Date:  2008-01-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8306882     Medline TA:  J Hypertens     Country:  England    
Other Details:
Languages:  eng     Pagination:  2093-9     Citation Subset:  IM    
Affiliation:
Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. mpirro@unipg.it
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MeSH Terms
Descriptor/Qualifier:
Adult
Adult Stem Cells / pathology*
Antigens, CD34 / metabolism
Base Sequence
Blood Cell Count
Case-Control Studies
DNA Primers / genetics
Down-Regulation
Endothelial Cells / pathology*
Female
Homeodomain Proteins / genetics*
Humans
Hypertension / blood*,  genetics*,  immunology
Male
Middle Aged
Neovascularization, Physiologic
Risk Factors
Chemical
Reg. No./Substance:
0/Antigens, CD34; 0/DNA Primers; 0/Homeodomain Proteins; 0/homeobox protein HOXA9

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