Abstract 752: HOXA9 and FLK1 Expression in CD34+ Peripheral Cells of Hypertensive Patients Correlates with the Number of Circulating Endothelial Progenitor Cells
Objective. HoxA9, a critical regulator of postnatal neovascularization and endothelial commitment during progenitor cell maturation, is essential for the expression of the endothelial-committed genes (ex. Flk1). We investigated whether in hypertensive patients CD34+ cells expression of HoxA9 and Flk1 is impaired and if a correlation exists between the expression of these genes and the number of circulating endothelial progenitor cells.
Methods and Results. 20 patients with never-treated essential hypertension and 20 age- and sex-matched normotensive controls were recruited for the study. Total RNA was isolated from circulating CD34+ cells and subjected to quantitative RT-PCR for measurement of HoxA9 and Flk1 expression. The number of endothelial progenitor cells was measured after PBMC isolation, staining with anti-CD34 and anti-Flk1 fluorescent antibodies and flow-citometry analysis. Hypertensive patients had a reduced percent expression of HoxA9 (−24%, p=0.001) and Flk1 (−15%, p=0.003) genes compared to normotensive subjects. In addition, the number of peripheral CD34+ cells and that of circulating endothelial progenitor cells was significantly lower in hypertensive than in normotensive subjects. Interestingly, a direct correlation was observed between the number of endothelial progenitors, on the one hand, CD34+ cells gene expression of HoxA9 (rho=0.31, p<0.05) and Flk1 (rho=0.42, p<0.05), on the other hand.
Conclusions. In hypertensive patients, a down-regulation of HoxA9 and Flk1 gene expression in peripheral CD34+ cells may contribute to reduce the number of circulating endothelial progenitors, thus potentially impairing postnatal neovascularization and vascular reparation.