Increased Transforming Growth Factor-β Production and Gene Expression by Peripheral Blood Monocytes of Hypertensive Patients

Abstract

Cultured human peripheral blood monocytes are known to secrete and express transforming growth factor-β (TGF-β), a multifunctional cytokine that can be involved in myocardial and vascular remodeling. In addition, monocytes/macrophages have been demonstrated to be colocalized with fibrosis of hypertrophied heart and in the vascular wall of hypertensive vessels. In this study, we tested TGF-β production and mRNA expression in peripheral blood monocytes from hypertensive patients with myocardial hypertrophy and increased carotid myointimal thickness with respect to healthy normotensive control subjects. We found an increased TGF-β activity in the conditioned medium of monocytes from hypertensive patients compared with control subjects as evaluated by inhibition of [³H]thymidine incorporation by mink lung epithelial cells (−83% and −18% in hypertensive and normotensive subjects;P<.001). Western blot analysis confirmed a significant difference in the amount of TGF-β protein secreted in the conditioned medium of hypertensive patients compared with that of normotensive subjects. Finally, we also observed a 4.2- and 5.5-fold increase in the amount of TGF-β₁and TGF-β₂transcripts, respectively. Our results indicate an upregulation of the TGF-β system in the peripheral blood monocytes of hypertensive patients with cardiovascular structural changes, suggesting a possible role of TGF-β monocyte production in hypertensive disease.