Transforming growth factor-β 1 hyperexpression in African-American hypertensives: A novel mediator of hypertension and/or target organ damage

Hypertension, a remediable risk factor for stroke, cardiovascular disease, and renal failure, affects 50 million individuals in the United States alone. African Americans (blacks) have a higher incidence and prevalence of hypertension and hypertension-associated target organ damage compared with Caucasian Americans (whites). Herein, we explored the hypotheses that transforming growth factor-β 1 (TGF-β 1 ) is hyperexpressed in hypertensives compared with normotensives and that TGF-β 1 overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-β 1 is hyperexpressed in blacks with end-stage renal disease compared with white end-stage renal disease patients and by the biological attributes of TGF-β 1 , which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-β 1 is produced in excess. TGF-β 1 profiles were determined in black and white hypertensive subjects and normotensive controls and included circulating protein concentrations, mRNA steady-state levels, and codon 10 genotype. Our investigation demonstrated that TGF-β 1 protein levels are highest in black hypertensives, and TGF-β 1 protein as well as TGF-β 1 mRNA levels are higher in hypertensives compared with normotensives. The proline allele at codon 10 (Pro 10 ) was more frequent in blacks compared with whites, and its presence was associated with higher levels of TGF-β 1 mRNA and protein. Our findings support the idea that TGF-β 1 hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.