Significant losses of nephrons due to various diseases in humans or subtotal nephrectomy in experimental animals trigger a cascade of events that lead to hypertension, oxidative stress, dyslipidemia, proteinuria, progressive glomerulosclerosis, tubulointerstitial injury, and eventually end-stage renal disease. The associated glomerulosclerosis and tubulointerstitial lesions are accompanied by and in part mediated by accumulation of lipids/lipoproteins and foam cell formation in the mesangium and tubulointerstitium of the diseased/remnant kidneys. In the tissue, macrophages remove modified lipoproteins via SR-A1 and extrude free cholesterol and phospholipids for uptake and disposal by HDL via adenosine triphosphate binding cassette A-1 (ABCA-1) transporter. In addition, these cells express SR-B1, which mediates bidirectional flux of cholesterol into and out of the cell. In view of the above considerations, we tested the hypothesis that accumulation of lipids and foam cell formation in the remnant kidney may be associated with dysregulation of the above receptors, which are central to the maintenance of cellular cholesterol balance. To this end, we determined protein abundance of ABCA-1, SR-A1, and SR-B1 (by Western blot analysis) in the kidney tissues of rats 6 week after 5/6 nephrectomy or sham operation. As expected renal mass reduction resulted in azotemia, hypertension, proteinuria, and increased serum total/HDL cholesterol concentration ratio. This was associated with severe reductions of ABCA-1 and a marked increase in SR-B1 but no significant change in SR-A1 abundance in the kidneys of rats with renal mass reduction compared to the control animals. In conclusion, renal mass reduction results in significant down-regulation of ABCA-1 protein abundance in the remnant kidney. This abnormality can contribute to glomerulosclerosis and tubulointerstitial injury by limiting HDL-mediated retrieval of surplus cholesterol and phospholipids from these tissues.
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