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Hyperuricemia is Associated with Increased Apo AI Fractional Catabolic Rates and Dysfunctional HDL in New Zealand Rabbits

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Lipids

Abstract

The potential cause–effect relationship between uric acid plasma concentrations and HDL functionality remains elusive. Therefore, this study aimed to explore the effect of oxonic acid (OA)-induced hyperuricemia on the HDL size distribution, lipid content of HDL subclasses, and apo AI turnover, as well as HDL functionality in New Zealand white rabbits. Experimental animals received OA 750 mg/kg/day by oral gavage during 21 days. The HDL-apo AI fractional catabolic rate (FCR) was determined by exogenous labeling with 125I, and HDL subclasses were determined by sequential ultracentrifugation and PAGE. Paraoxonase-1 activity (PON-1) and the effect of HDL on relaxation of aorta rings in vitro were determined as an indication of HDL functionality. Oxonic acid induced a sixfold increase of uricemia (0.84 ± 0.06 vs. 5.24 ± 0.12 mg/dL, P < 0.001), and significant decreases of triglycerides and phospholipids of HDL subclasses, whereas HDL size distribution and HDL-cholesterol remained unchanged. In addition, HDL-apo AI FCR was significantly higher in hyperuricemic rabbits than in the control group (0.03697 ± 0.0038 vs. 0.02605 ± 0.0017 h−1 respectively, P < 0.05). Such structural and metabolic changes were associated with lower levels of PON-1 activities and deleterious effects of HDL particles on endothelium-mediated vasodilation. In conclusion, hyperuricemia is associated with structural and metabolic modifications of HDL that result in impaired functionality of these lipoproteins. Our data strongly suggest that uric acid per se exerts deleterious effects on HDL that contribute to increase the risk of atherosclerosis.

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Abbreviations

C:

Cholesterol

CAD:

Coronary artery disease

FCR:

Fractional catabolic rate

HDL:

High-density lipoproteins

HU:

Hyperuricemia

OA:

Oxonic acid

PAGE:

Polyacrylamide gradient gel electrophoresis

PL:

Phospholipids

PR:

Production rate

Tg:

Triglycerides

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Acknowledgements

This study was supported by CONACYT, Project No. 132473 (to O. P.-M.). M. M.-R. was a recipient of a CONACYT grant.

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Authors and Affiliations

  1. Department of Molecular Biology, Instituto Nacional de Cardiología “Ignacio Chávez”, Juan Badiano 1, Sección XVI, 14080, Mexico City, Mexico

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

  2. Nephrology Department, Instituto Nacional de Cardiología “Ignacio Chávez”, Mexico City, Mexico

    L. Gabriela Sánchez-Lozada, Fernando E. García-Arroyo & Martha Franco

Authors
  1. Miriam Martínez-Ramírez
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  2. Cristóbal Flores-Castillo
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  3. L. Gabriela Sánchez-Lozada
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  8. Fernando E. García-Arroyo
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  13. Oscar Pérez-Méndez
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Correspondence to Oscar Pérez-Méndez.

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Martínez-Ramírez, M., Flores-Castillo, C., Sánchez-Lozada, L.G. et al. Hyperuricemia is Associated with Increased Apo AI Fractional Catabolic Rates and Dysfunctional HDL in New Zealand Rabbits. Lipids 52, 999–1006 (2017). https://doi.org/10.1007/s11745-017-4301-y

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