Reduced number of circulating endothelial progenitors and HOXA9 expression in CD34+ cells of hypertensive patients.
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.
Pirro
Matteo
M
Unit of Internal Medicine, Angiology and Arteriosclerosis Diseases, Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy. mpirro@unipg.it
Schillaci
Giuseppe
G
Menecali
Cinzia
C
Bagaglia
Francesco
F
Paltriccia
Rita
R
Vaudo
Gaetano
G
Mannarino
Massimo R
MR
Mannarino
Elmo
E
D000328:Adult; D053687:Adult Stem Cells / Q000473:pathology*; D018952:Antigens, CD34 / Q000378:metabolism; D001483:Base Sequence; D001772:Blood Cell Count; D016022:Case-Control Studies; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D042783:Endothelial Cells / Q000473:pathology*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D012307:Risk Factors
D018952:Antigens, CD34; D017931:DNA Primers; D018398:Homeodomain Proteins; C097899:homeobox protein HOXA9