ACE inhibitors attenuate expression of renal transforming growth factor-beta 1 in humans

Progressive nephropathies are characterized by the enhanced accumulation of extracellular matrix in the kidney. Overproduction of transforming growth factor-beta (TGF-beta) was shown to result in pathological tissue fibrosis through the accumulation of extracellular matrix proteins. it has been prop osed that angiotensin II stimulates TGF-beta production. Despite accumulati ng data supporting the effects of angiotensin-converting enzyme (ACE) inhib itors on the attenuation of TGF-beta in vitro and in rats, such studies in humans are lacking. The present study sought to determine the effects of AC E inhibitors on TGF-beta1 in patients with glomerulonephritis. Using compet itive polymerase chain reaction and the sandwich enzyme-linked immunosorben t assay, TGF-beta1 messenger RNA (mRNA) abundance and TGF-beta1 protein lev els were measured. Patients with immunoglobulin A nephropathy administered ACE inhibitors showed significantly lower renal TGF-beta1 gene expression t han patients not administered these medications (mean ratios of TGF-beta1/b eta -actin, 4.27 +/- 0.62 [SEM] versus 14.81 +/- 3.81; P < 0.05), whereas n o difference was noted between patients administered ACE inhibitors and hea lthy controls (4.27 +/- 0.62 versus 2.78 +/- 0.71). ACE inhibitor therapy d id not affect TOP-<beta>1 mRNA expression in freshly isolated mononuclear c ells. Urine and serum TGF-beta1 protein levels were not affected by the adm inistration of ACE inhibitors. However, possibly a longer duration of treat ment would decrease TGF-beta1 levels in urine or blood. In conclusion, we o bserved a significant reduction in TGF-beta1 expression in the kidney, by A CE inhibitors, and this suggests that the effects of ACE inhibitors observe d in animals can be extrapolated to patients with chronic renal disease. (C ) 2000 by the National Kidney Foundation, Inc.