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Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits

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Lipids

Abstract

The catabolism and structure of high-density lipoproteins (HDL) may be the determining factor of their atheroprotective properties. To better understand the role of the kidney in HDL catabolism, here we characterized HDL subclasses and the catabolic rates of apo A-I in a rabbit model of proteinuria. Proteinuria was induced by intravenous administration of doxorubicin in New Zealand white rabbits (n = 10). HDL size and HDL subclass lipids were assessed by electrophoresis of the isolated lipoproteins. The catabolic rate of HDL-apo A-I was evaluated by exogenous radiolabelling with iodine-131. Doxorubicin induced significant proteinuria after 4 weeks (4.47 ± 0.55 vs. 0.30 ± 0.02 g/L of protein in urine, P < 0.001) associated with increased uremia, creatininemia, and cardiotoxicity. Large HDL2b augmented significantly during proteinuria, whereas small HDL3b and HDL3c decreased compared to basal conditions. HDL2b, HDL2a, and HDL3a subclasses were enriched with triacylglycerols in proteinuric animals as determined by the triacylglycerol-to-phospholipid ratio; the cholesterol content in HDL subclasses remained unchanged. The fractional catabolic rate (FCR) of [131I]-apo A-I in the proteinuric rabbits was faster (FCR = 0.036 h−1) compared to control rabbits group (FCR = 0.026 h−1, P < 0.05). Apo E increased and apo A-I decreased in HDL, whereas PON-1 activity increased in proteinuric rabbits. Proteinuria was associated with an increased number of large HDL2b particles and a decreased number of small HDL3b and 3c. Proteinuria was also connected to an alteration in HDL subclass lipids, apolipoprotein content of HDL, high paraoxonase-1 activity, and a rise in the fractional catabolic rate of the [131I]-apo A-I.

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Abbreviations

ARE:

Arylesterase

CHD:

Coronary heart disease

FCR:

Fractional catabolic rate

HDL:

High-density lipoproteins

LPL:

Lipoprotein lipase

LVEF:

Left ventricular ejection fraction

PL:

Phospholipid

PON-1:

Paraoxonase-1

TAG:

Triacylglycerols

TC:

Total cholesterol

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Acknowledgments

This study was supported by a CONACYT Grant No. 132473. We are grateful to Rodrigo Velázquez Espejel for his technical support.

Author information

Authors and Affiliations

  1. Molecular Biology Department, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Section XVI, 14080, México D.F., Mexico

    Victoria López-Olmos, Elizabeth Carreón-Torres, María Luna-Luna, Cristobal Flores-Castillo, Miriam Martínez-Ramírez, Rocío Bautista-Pérez, Mónica Muñoz-Vega, José-Manuel Fragoso, Gilberto Vargas-Alarcón & Oscar Pérez-Méndez

  2. Atherosclerosis Study Group, Instituto Nacional de Cardiología “Ignacio Chávez”, México D.F., Mexico

    Elizabeth Carreón-Torres, Rocío Bautista-Pérez, Martha Franco, Julio Sandoval-Zárate, José-Manuel Fragoso, Gilberto Vargas-Alarcón & Oscar Pérez-Méndez

  3. Nephrology Department, Instituto Nacional de Cardiología “Ignacio Chávez”, México D.F., Mexico

    Martha Franco

  4. Cardiopulmonary Department, Instituto Nacional de Cardiología “Ignacio Chávez”, México D.F., Mexico

    Julio Sandoval-Zárate

  5. Outpatient Care Department, Instituto Nacional de Cardiología “Ignacio Chávez”, México D.F., Mexico

    Francisco-Javier Roldán

  6. Pathology Department, Instituto Nacional de Cardiología “Ignacio Chávez”, México D.F., Mexico

    Alberto Aranda-Fraustro & Elizabeth Soria-Castro

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  1. Victoria López-Olmos
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  2. Elizabeth Carreón-Torres
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  3. María Luna-Luna
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  4. Cristobal Flores-Castillo
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  6. Rocío Bautista-Pérez
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  7. Martha Franco
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  8. Julio Sandoval-Zárate
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  9. Francisco-Javier Roldán
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  10. Alberto Aranda-Fraustro
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  12. Mónica Muñoz-Vega
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  13. José-Manuel Fragoso
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  14. Gilberto Vargas-Alarcón
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  15. Oscar Pérez-Méndez
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Correspondence to Oscar Pérez-Méndez.

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López-Olmos, V., Carreón-Torres, E., Luna-Luna, M. et al. Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits. Lipids 51, 311–320 (2016). https://doi.org/10.1007/s11745-016-4120-6

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