PMID- 10752526
OWN - NLM
STAT- MEDLINE
DCOM- 20000606
LR  - 20210511
IS  - 1046-6673 (Print)
IS  - 1046-6673 (Linking)
VI  - 11
IP  - 4
DP  - 2000 Apr
TI  - Early mechanisms of renal injury in hypercholesterolemic or hypertriglyceridemic 
      rats.
PG  - 669-683
LID - 10.1681/ASN.V114669 [doi]
AB  - Hyperlipidemia in conjunction with uninephrectomy leads to renal injury in rats. 
      It is unknown whether this is due to mesangial cell or podocyte injury and 
      whether the injuries induced by hypercholesterolemia and hypertriglyceridemia 
      share a similar pathogenesis. Therefore, renal effects of hypercholesterolemia 
      were studied in male rats with dietary hypercholesterolemia compared with rats on 
      a regular diet. Renal effects of hypertriglyceridemia were studied in female 
      Nagase analbuminemic rats (NAR). Hypertriglyceridemia was reduced in NAR by 
      ovariectomy. Both models were studied after uninephrectomy or sham operation. 
      Dietary hypercholesterolemia had little effect on plasma triglycerides, whereas 
      ovariectomy in the NAR had no effect on plasma cholesterol. However, an increase 
      in intermediate density lipoprotein cholesterol was common to both models. 
      Dietary hypercholesterolemia and uninephrectomy separately induced a similar 
      increase in proteinuria after 13 wk, which was additive when these interventions 
      were combined. At this stage, only a minimal increase was present in glomerular 
      alpha-smooth muscle actin staining, a marker of mesangial cell activation, or in 
      mesangial matrix expansion. Moreover, platelet-derived growth factor-B chain, a 
      marker of mesangial cell proliferation, was not increased. However, podocyte 
      injury was prominent as evidenced by podocytic de novo expression of desmin and 
      ultrastructural changes. Glomerular macrophage counts were increased by 
      hypercholesterolemia but not by uninephrectomy, and were not related to the level 
      of proteinuria. Hypertriglyceridemia and uninephrectomy in female NAR induced an 
      increase in proteinuria after 24 wk, which was also associated with an increase 
      in podocyte desmin expression without any mesangial activation and proliferation 
      or matrix accumulation. Hypertriglyceridemia, proteinuria, and the increase in 
      desmin staining were largely prevented by ovariectomy. Interstitial myofibroblast 
      activation and tubulointerstitial injury accompanied proteinuria in both models. 
      These findings indicate that both hypercholesterolemia and hypertriglyceridemia 
      aggravate renal injury primarily via podocyte rather than via mesangial cell 
      damage. Such podocyte injury is accompanied by tubulointerstitial cell activation 
      and injury.
FAU - Joles, Jaap A
AU  - Joles JA
AD  - Department of Nephrology and Hypertension, University Medical Center, Utrecht, 
      The Netherlands.
FAU - Kunter, Uta
AU  - Kunter U
AD  - Department of Internal Medicine, Medical School, Aachen, Germany.
FAU - Janssen, Ulf
AU  - Janssen U
AD  - Department of Internal Medicine, Medical School, Aachen, Germany.
FAU - Kriz, Wilhelm
AU  - Kriz W
AD  - Laboratory of Anatomy and Cell Biology, Heidelberg University, Germany.
FAU - Rabelink, Ton J
AU  - Rabelink TJ
AD  - Department of Nephrology and Hypertension, University Medical Center, Utrecht, 
      The Netherlands.
FAU - Koomans, Hein A
AU  - Koomans HA
AD  - Department of Nephrology and Hypertension, University Medical Center, Utrecht, 
      The Netherlands.
FAU - Floege, Jurgen
AU  - Floege J
AD  - Department of Internal Medicine, Medical School, Aachen, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Am Soc Nephrol
JT  - Journal of the American Society of Nephrology : JASN
JID - 9013836
RN  - 0 (Serum Albumin)
SB  - IM
MH  - Animals
MH  - Female
MH  - Glomerulosclerosis, Focal Segmental/etiology/pathology
MH  - Hypercholesterolemia/blood/*complications/pathology/physiopathology
MH  - Hypertriglyceridemia/blood/*complications/pathology/physiopathology
MH  - Immunologic Techniques
MH  - Kidney/pathology/physiopathology
MH  - Kidney Diseases/*etiology/prevention & control
MH  - Male
MH  - Nephrectomy
MH  - Nephritis, Interstitial/etiology/pathology
MH  - Ovariectomy
MH  - Rats
MH  - Rats, Mutant Strains/genetics
MH  - Rats, Sprague-Dawley
MH  - Serum Albumin/deficiency/genetics
MH  - Time Factors
EDAT- 2000/04/07 09:00
MHDA- 2000/06/10 09:00
CRDT- 2000/04/07 09:00
PHST- 2000/04/07 09:00 [pubmed]
PHST- 2000/06/10 09:00 [medline]
PHST- 2000/04/07 09:00 [entrez]
AID - 11/4/669 [pii]
AID - 10.1681/ASN.V114669 [doi]
PST - ppublish
SO  - J Am Soc Nephrol. 2000 Apr;11(4):669-683. doi: 10.1681/ASN.V114669.