RECOVERY OF DAMAGED GLOMERULAR CAPILLARY NETWORK WITH ENDOTHELIAL-CELL APOPTOSIS IN EXPERIMENTAL PROLIFERATIVE GLOMERULONEPHRITIS

Capillary repair can occur in damaged glomeruli in recovery models of glomerulonephritis (GN). In order to clarify whether capillary repair is an essential component in glomerular recovery from GN, we have exam ined the development of the capillary repair after inflammatory injury in both the repairing glomeruli and the segmental sclerotic scar lesi ons in Thy-1 GN. Mesangiolytic glomerular damage was induced in rats w ith anti-Thy-1.1 antibody administration. Diffuse mesangiolysis and se gmental microaneurysmal ballooning developed in damaged glomeruli by d ay 3, with reduction of endothelial cellularity. Thereafter, histologi cal proliferative GN developed between day 5 and week 3. Endothelial c ell proliferation began on day 1 and peaked on day 5, and the number o f glomerular endothelial cells increased and exceeded the level of con trol values on day 7. Angiogenic glomerular capillary repair occurred through the process of not only capillary regeneration from remaining endothelial cells in capillary aneurysmal lesions but also new capilla ry growth derived from the glomerular vascular poles by day 7. The num ber of glomerular capillary lumina also increased to the level of cont rols by week 3. Subsequently, mesangial proliferative GN resolved, and most of the glomeruli recovered to their normal structure with the re construction of the capillary network by weeks 4-6. In the glomerular capillary repair, significant apoptosis of glomerular endothelial cell s was present during the period of mild endothelial cell hypercellular ity between day 7 and day 10 (0.06 +/- 0.02 apoptotic endothelial cell s/glomerular cross section vs. 0.00 +/- 0.00 in controls, mean +/- SEM ; p < 0.05. In Thy-1 GN, most of the damaged glomeruli recovered with angiogenic capillary repair. However, segmental sclerotic scar lesions remained in 10-30% of the glomeruli with an incomplete repair of glom erular capillaries. Therefore, it is concluded that following the dest ruction of the glomerular capillary network in GN, angiogenic capillar y repair plays an essential role in the recovery of damaged glomeruli, and incomplete capillary repair leads to sclerotic scar lesions in da maged glomeruli. Glomerular capillary repair occurs through the proces s of capillary regeneration from remaining endothelial cells as well a s new glomerular capillary growth from the glomerular vascular poles. In glomerular capillary repair, apoptosis is necessary in regulating t he number of intrinsic endothelial cells.