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Total Outflow of High-Density Lipoprotein-Cholesteryl Esters from Plasma Is Decreased in a Model of 3/4 Renal Mass
María Luna-Luna1, Martha Franco2, Elizabeth Carreón-Torres1
1Department of Molecular Biology, Instituto Nacional de Cardiologia "Ignacio Chavez", Mexico City 14080, Mexico.
Insights
Reduced kidney function in rabbits led to higher cholesteryl esters in high-density lipoproteins (HDL). This suggests kidneys play a role in regulating HDL lipid content and cholesterol homeostasis.
Area of Science:
- Nephrology
- Lipid Metabolism
- Cardiovascular Research
Background:
- Previous studies suggest kidneys influence high-density lipoprotein (HDL) cholesterol homeostasis.
- The precise role of renal function in lipoprotein metabolism remains debated.
Purpose of the Study:
- To investigate the impact of reduced renal mass on HDL cholesteryl ester turnover.
- To elucidate the kidney's role in regulating HDL lipid content.
Main Methods:
- Characterized HDL subclasses in rabbits with 75% reduced renal mass (Ntx).
- Studied plasma HDL cholesteryl ester kinetics using tritium labeling.
- Analyzed cholesteryl ester exchange between HDL and VLDL/LDL.
Main Results:
- Reduced renal mass resulted in cholesteryl ester enrichment in HDL subclasses.
- Cholesteryl ester exchange between HDL and apo B-lipoproteins was unchanged.
- A decreased fractional catabolic rate (FCR) of HDL cholesteryl esters was observed in Ntx rabbits.
Conclusions:
- Kidney mass reduction alters HDL lipid composition.
- The kidneys' reduced capacity to catabolize HDL cholesteryl esters contributes to their accumulation.
- Findings support a role for the kidneys in cholesterol homeostasis via HDL metabolism.
Abstract:
(1) Background: Previous studies have enriched high-density lipoproteins (HDL) using cholesteryl esters in rabbits with a three-quarter reduction in functional renal mass, suggesting that the kidneys participate in the cholesterol homeostasis of these lipoproteins. However, the possible role of the kidneys in lipoprotein metabolism is still controversial. To understand the role of the kidneys in regulating the HDL lipid content, we determined the turnover of HDL-cholesteryl esters in rabbits with a three-quarter renal mass reduction. (2) Methods: HDL subclass characterization was conducted, and the kinetics of plasma HDL-cholesteryl esters, labeled with tritium, were studied in rabbits with a 75% reduction in functional renal mass (Ntx). (3) Results: The reduced renal mass triggered the enrichment of cholesterol, specifically cholesteryl esters, in HDL subclasses. The exchange of cholesteryl esters between HDL and apo B-containing lipoproteins (VLDL/LDL) was not significantly modified in Ntx rabbits. Moreover, the cholesteryl esters of HDL and VLDL/LDL fluxes from the plasmatic compartment tended to decrease, but they only reached statistical significance when both fluxes were added to the Nxt group. Accordingly, the fractional catabolic rate (FCR) of the HDL-cholesteryl esters was lower in Ntx rabbits, concomitantly with its accumulation in HDL subclasses, probably because of the reduced mass of renal cells requiring this lipid from lipoproteins.
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