Hypertension-induced organ damage in African Americans: transforming growth factor-beta(1) excess as a mechanism for increased prevalence.
Hypertension is prevalent world-wide, and it affects over 50 million individuals in the United States alone. African Americans (blacks) have a high prevalence of hypertension, develop it at an earlier age, and suffer excessively from severe or malignant hypertension. They also have a high prevalence of target organ damage attributable to hypertension, including left ventricular hypertrophy, stroke, end-stage renal disease (ESRD) and coronary artery disease. Hypertensive nephrosclerosis is particularly more prevalent in blacks compared to whites, and there is evidence that factors in addition to elevated blood pressure contribute to its pathogenesis. Transforming growth factor-beta 1 (TGF-beta1) is a fibrogenic cytokine that has been implicated in the development and progression of experimental and human renal diseases. We have demonstrated that blacks with ESRD have higher circulating levels of TGF-beta1 protein compared to whites with ESRD. We have also found that hyperexpression of TGF-beta1 is more frequent in blacks with hypertension than in whites. We propose that TGF-beta1 hyperexpression may be an important mediator of hypertension and hypertensive nephrosclerosis. We hypothesize also that the increased frequency of TGF-beta1 hyperexpression may contribute to the excess burden of ESRD in blacks. Based on our hypotheses, and the observations that angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists reduce angiotensin II-mediated stimulation of TGF-beta1 production, we propose that treatment with these agents might be efficacious in preventing or slowing the progression of target organ damage in hypertensive blacks.
August
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Divisions of Nephrology and Hypertension, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA. paugust@med.cornell.edu
Leventhal
B
B
Suthanthiran
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M
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D044383:Black People; D003327:Coronary Disease / Q000208:ethnology; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000150:complications / Q000188:drug therapy / Q000208:ethnology*; D017379:Hypertrophy, Left Ventricular / Q000208:ethnology / Q000209:etiology; D007676:Kidney Failure, Chronic / Q000097:blood / Q000208:ethnology* / Q000209:etiology / Q000517:prevention & control; D016014:Linear Models; D015995:Prevalence; D020521:Stroke / Q000208:ethnology; D016212:Transforming Growth Factor beta / Q000097:blood* / Q000502:physiology; D044465:White People; D001741:Black or African American
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D016212:Transforming Growth Factor beta; D000804:Angiotensin II