- The Effects of Angiotensin Converting Enzyme Inhibitor on Progressive Glomerular Sclerosis.
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Mi Ok Park, Yong Jin Kim, Hoon Kyu Oh, Chul Ho Lee, Byung Hwa Hyun, Jung Sik Kwak
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Korean J Pathol. 1998;32(12):1058-1065.
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 Abstract
- Almost all advanced glomerular diseases have glomerular sclerotic changes to varying degrees whatever causes their primary glomerular disease are. Pathogenesis of these sclerosis has been thought of as the hyperfiltration in the primary glomerulosclerosis due to development of glomerular hypertension in each insulted glomeruli. This background gave the theoretical bases for antihypertensive therapies for supporting chronic renal insufficient patients.
Angiotensin converting enzyme (ACE) inhibitor, one of the antihypertensive drugs, has received attention recently for its effectiveness. The aims of this study determined the effects and mechanism of the ACE inhibitor, enalapril, on the glomerulosclerosis in FGS/NgaKist mice, which was an animal model of chronic renal failure by generating spontaneously heavy proteinuria and progressive glomerulosclerosis. Five-week-old FGS/NgaKist mice (n=38) were assigned to four groups. Group 1a (n=6) and group 2a (n=8) fed with a vehicle, were sacrificed at the end of 10 weeks and 15 weeks, respectively. Group 1b (n=12) and 2b (n=12) received enalapril (100 mg/L) in drinking water for 5 weeks and 10 weeks from 6th week of age respectively, and were sacrified on the same day as the control groups. Doses of enanapril were maintained to 2 mg/kg/day by measuring the amount of water consumption. In enalapril groups 1b and 2b, systemic blood pressure (74.7 14.0 mm Hg, 74.3 15.9 mmHg) were significantly lower than control group 2a (116.1 4.6 mmHg, P<0.001). Similarly, degree of proteinuria lowered in enalapril group 2b versus control group 2a (0% and 50.0%, P<0.001). Glomerulosclerosis percentage significantly decreased (P<0.001) (group 1b and 2b; 1.9 6.5, 5.6 7.0 vs control 1a and 2a; 32.8 15.5, 31.4 13.8). Glomerulosclerosis score also decreased (P<0.001) (group 1b and 2b; 0.02 0.08 vs control 1a and 2a; 0.48 0.12, 0.30 0.14). The immunofluorescent staining of enalapril groups showed negative for mesangial deposition of IgG, IgA, IgM, and C3 which were positive in control groups. Immunohistochemical staining with TGF-beta1 was negative in enalapril groups and sclerotic glomeruli both enalapril groups and control groups. These results support that the ACE inhibitor has a renoprotective effect on glomerulosclerosis not only by decreasing the blood pressure but also by suppressing the immune deposits on glomeruli.
- Expression of Transforming Growth Factor-beta and Morphologic Changes of Glomerulosclerosis in FGS/NgaKist Mouse.
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Hoon Kyu Oh, Yong Jin Kim, Mi Ok Park, Chul Ho Lee, Byung Hwa Hyun, In Soo Shu
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Korean J Pathol. 1998;32(1):35-42.
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Abstract
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- Focal segmental glomerulosclerosis (FSGS) is presented as not only one of the primary glomerular diseases but also as a secondary phenomenon for chronic irreversible renal diseases. The main pathological feature of FSGS is the accumulation of extracellular matrix in the glomeruli, for which overexpression of transforming growth factor-beta (TGF-beta) may be responsible for the accumulation of pathological matrix. A new animal model (FGS/NgaKist mouse) of renal failure by spontaneously generating glomerulosclerosis was developed. To elucidate the role of TGF-beta for FSGS, authors observed glomeruli of FGS/NgaKist mouse periodically. FGS/NgaKist mouse strain showed progression of proteinuria and focal glomerular sclerosis with the aging. The glomeruli showed anti IgG, IgA, IgM and complement complex deposits and extracellular matrix accumulation in the mesangium. TGF-beta mRNA and beta2antibody expressions were increased with the advance of glomerular sclerosis. The results suggest the following; FSGS of FGS/NgaKist strain is immune mediated disease and this stimuli on mesangial or endothelial cells may activate TGF-beta gene in their nuclei. This activation, in turn, can cause sclerosis by increasing TGF-beta mRNA transcription followed by secretion of TGF-beta and its action as cytokine for making collagen fibrils.
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