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

Abstract

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-␤1 (TGF-␤1) is hyperexpressed in hypertensives compared with normotensives and that TGF-␤1 overexpression is more frequent in blacks compared with whites. These hypotheses were stimulated by our recent demonstration that TGF-␤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-␤1, which include induction of endothelin-1 expression, stimulation of renin release, and promotion of vascular and renal disease when TGF-␤ 1 is produced in excess. TGF-␤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-␤1 protein levels are highest in black hypertensives, and TGF-␤1 protein as well as TGF-␤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-␤1 mRNA and protein. Our findings support the idea that TGF-␤ 1 hyperexpression is a risk factor for hypertension and hypertensive complications and provides a mechanism for the excess burden of hypertension in blacks.

Long-chain polyunsaturated fatty acids interact with nitric oxide, superoxide anion, and transforming growth factor-β to prevent human essential hypertension

“…Recently, circulating levels of transforming growth factor-b (TGF-b) were found to be elevated in hypertensives compared with normotensives (Suthanthiran et al, 2000;Derhaschnig et al, 2002). Both systolic and diastolic blood pressure was significantly higher in individuals with the CC genotype of TGF-b (869T-C) compared to those with the TT or TC genotype, suggesting that the TGF-b1 gene could be a candidate susceptibility locus for hypertension (Yamada et al, 2002).…”

Hypertension in black people: pathophysiology and therapeutic aspects

“…8 TGF-beta was found to be hyperexpressed in black patients with hypertension. 9 Alterations in the renal haemodynamics may also contribute to the higher risk of hypertensive nephropathy in black subjects. 10,11 …”

TGF-β1 Gene Polymorphisms and Peritoneal Equilibration Test Results in CAPD Patients

“…[6,7,12,13,[23][24][25] It is not clear yet which alleles cause higher amounts of the TGF-β1 protein.…”

“…[5] TGF-β1-induced fibroblast proliferation, stimulation of collagen synthesis, and enhanced matrix accumulation contribute to the development of fibrogenesis. [6,7] TGF-βl gen polymorphisms in the signal sequence genetically may be responsible for increased TGFβl production. Seven polymorphisms in the TGF-βl gene have been reported in a great number of studies.…”