Cholesterol Feeding Following Unilateral Nephrectomy in the Rat Leads to Glomerular Hypertrophy

Rayner, Hugh; Ward, Lianne; Walls, John

doi:10.1159/000186349

Cited by 27 publications

(13 citation statements)

References 6 publications

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“…On the basis of these reports, it seems possible that the segmental clusters of foam cells associated with capsular adhesions and the destruction of the glomerular tuft observed in our model may represent injury to cells caused by several toxic products released during the phagocytosis of lipids by infiltrating glomerular macrophages. A similar putative mechanism has recently been reported by Rayneret al [39]. Thus, it appears that macrophages that infiltrate the glome ruli play a very important role in the development of glome rular injury in our model.…”

Section: Discussionsupporting

confidence: 90%

Characteristic Glomerular Lesions in the ExHC Rat: A Unique Model for Lipid-lnduced Glomerular Injury

Hattori¹,

Yamaguchi

Kawaguchi³

et al. 1993

Nephron

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ExHC rats were bred from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. Although chemical and histological examination of the aorta from ExHC rats fed a diet containing 3% cholesterol, 0.6% sodium cholate and 15% olive oil (high-cholesterol diet, HCD) has been reported, renal injury in this model has not been investigated to date. Therefore, we examined the renal pathological changes and proteinuria in this model. ExHC rats fed an HCD developed proteinuria and characteristic glomerular lesions within 4-8 weeks after initiation of the diet. The most striking glomerular change observed in this model was the marked accumulation of numerous lipid-filled foam cells, with a surface marker that identified them as macrophages, within the mesangial regions which could have been involved in focal and segmental glomerular sclerosis. Our study demonstrates that ExHC rats fed a cholesterol-supplemented diet develop glomerular injury that may be mediated by infiltrating macrophages. These results imply that ExHC rats may be well-suited for the use in investigations of the role of macrophages in the pathogenesis of lipid-induced glomerular injury.

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Section: Discussionsupporting

confidence: 90%

Characteristic Glomerular Lesions in the ExHC Rat: A Unique Model for Lipid-lnduced Glomerular Injury

Hattori¹,

Yamaguchi

Kawaguchi³

et al. 1993

Nephron

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show abstract

“…On the basis of these reports, it seems possible that the segmental clusters of foam cells that are associated with capsular adhesions and the destruction of the glomeru lar tufts observed in this model may represent injury to cells that is caused by various toxic products released during the foam-cell transformation of infiltrating glomerular macro phages. A similar putative mechanism has been suggested by Rayner et al [13]. Oxi-LDL has been shown to be cytotoxic to mesangial cells [57], and this property may account for the absence of expansion of the mesangial matrix and the increased number of mesangial cells in this model.…”

Section: Discussionsupporting

confidence: 82%

“…Gupta et al [47] showed that native, oxidized and glycated LDL all bind to a considerable extent to the extracellular matrix that is gener ated by rat mesangial cells in culture. Indeed, it has been demonstrated in man and in experimental models of renal disease that mesangial deposition of P-VLDL and apolipoproteins B and E occurs [7,13,48], Although whether the glomerular endothelium and glomerular macrophages con tribute to the oxidative modification of lipoproteins is un known, mesangial cells appear to have the capacity to generate the reactive oxygen molecules that are necessary to initiate the peroxidation of lipids [49][50][51]. Taken together with previous reports, the results of our present study sug gest the possibility that local glomerular oxidative modifi cation of lipoproteins might occur in vivo and contribute to the development of foam cells within glomeruli.…”

Section: Discussionmentioning

confidence: 99%

Probucol Reduces Renal Injury in the ExHC Rat

Hattori¹,

Ito²,

Kawaguchi³

et al. 1994

Nephron

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To investigate the potential roles of oxidized lipoproteins and glomerular macrophages in the pathogenesis of lipid-induced glomerular injury, we examined the effects of administration of probucol on the development of renal injury in ExHC rats. ExHC rats are derived from the Sprague-Dawley strain and are highly susceptible to dietary hypercholesterolemic stimuli. We reported previously that ExHC rats fed a cholesterol-supplemented diet (HCD) develop proteinuria and characteristic glomerular lesions. These lesions include marked accumulation of numerous lipid-filled foam cells, which have a surface marker that identifies them as macrophages, within mesangial regions, as well as segmental clusters of foam cells that are associated with capsular adhesions, the destruction of glomerular tufts and glomerular sclerosis. ExHC rats were maintained on an HCD or on an HCD supplemented with 5% (wt/wt) probucol for 8 weeks. Probucol reduced the extent of renal injury, as evidenced by proteinuria and segmental glomerular lesions, in ExHC rats fed an HCD, in the absence of any significant reduction in plasma cholesterol levels. Both low-density lipoprotein and β-very-low density lipoprotein isolated from the plasma of probucol-treated rats were found to be resistant to oxidative modification by cupric ions. Both the size and the number of foam cells within glomeruli in the probucol-treated rats were significantly reduced as compared to those of foam cells in the untreated rats. Probucol might reduce renal injury in ExHC rats by limiting the oxidative modification of lipoproteins and, subsequently, by restricting the foam cell transformation of macrophages within glomeruli and by inhibiting the recruitment of macrophages into glomeruli. The results of the present study may be interpreted to indicate that local glomerular oxidative modification of lipoproteins might occur in vivo, and both oxidized lipoproteins and glomerular macrophages may play important roles in the pathogenesis of lipid-induced glomerular injury.

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“…These observations were similar to those reported in other vascular tissues [20][21][22][23] and renal microvessels [24] in response to cholesterol feeding or to spontaneous hyperlipidemia. In contrast to some earlier reports [26][27][28], lipid accumulation in the mesangium was not seen in the present study. The ability to demon strate neutral lipids in the glomeruli of animals exposed to a high-cholesterol diet may depend on the duration of lip id exposure, and it is possible that lipid accumulation in the mesangial area may occur as a later event.…”

Section: Discussioncontrasting

confidence: 99%

Effect of Dietary Cholesterol on Rat Glomerular Cholesterol Esterase

et al. 1993

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The accumulation of tissue cholesterol and cholesteryl esters is commonly seen during the development of both atherosclerosis and glomerulosclerosis. The intracellular cholesterol content is regulated, in part, by the hydrolysis of cholesteryl esters to cholesterol, a reaction catalyzed by cholesterol esterase. Decreased cholesterol esterase has been linked to cholesteryl ester accumulation in vascular cells and has been postulated to be an important factor in the progression of atherosclerosis and, possibly, glomerulosclerosis. In order to determine whether cholesterol esterase regulates glomerular cholesterol accumulation, the effect of cholesterol feeding on the cholesterol content and the activity of cholesterol esterase was examined in rat glomeruli. Cholesterol esterase was measured using a cholesteryl [1-¹⁴C]oleatelecithin liposome substrate. Total and free glomerular cholesterol was measured spectrofluorometrically. Feeding rats 4% cholesterol for 2 months decreased total glomerular (acid plus neutral) cholesterol esterase activity when compared to glomeruli from similar rats fed a normal chow (1.8 ± 0.1 versus 1.48 ± 0.2 nmol/mg protein/h, p < 0.05). Total, free and esterified cholesterol concentrations were higher in glomeruli from cholesterol-fed rats than from controls, consistent with decreased cholesterol esterase activity. Thus, glomerular cholesterol accumulation appears to be regulated by cholesterol esterase. This finding is similar to that in other vascular tissues which have been investigated and which are prone to accumulate cholesterol during the development of atherosclerosis.

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Cholesterol Feeding Following Unilateral Nephrectomy in the Rat Leads to Glomerular Hypertrophy

Cited by 27 publications

References 6 publications

Characteristic Glomerular Lesions in the ExHC Rat: A Unique Model for Lipid-lnduced Glomerular Injury

Characteristic Glomerular Lesions in the ExHC Rat: A Unique Model for Lipid-lnduced Glomerular Injury

Probucol Reduces Renal Injury in the ExHC Rat

Effect of Dietary Cholesterol on Rat Glomerular Cholesterol Esterase

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