A triglyceride-rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model.
Clin Exp Immunol
; 192(3): 337-347, 2018 06.
Article
in En
| MEDLINE
| ID: mdl-29405270
ABSTRACT
Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper-TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68+ macrophages. The hypersensitive response to ANTN was not seen in low-density lipoprotein receptor knock-out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P-407. These data indicate that a hyper-TGRL state might be more detrimental to the kidneys than low-density lipoprotein-driven hypercholesterolaemia during immune complex-mediated nephritis. We speculate that the hyper-TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Triglycerides
/
Acute Kidney Injury
/
Hypercholesterolemia
/
Lipoproteins
/
Macrophages
/
Nephritis
Type of study:
Prognostic_studies
/
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
Clin Exp Immunol
Year:
2018
Document type:
Article
Affiliation country:
Reino Unido