title: Increased HDL Size and Enhanced Apo A-I Catabolic Rates Are Associated With Doxorubicin-Induced Proteinuria in New Zealand White Rabbits.
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 [(131)I]-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 [(131)I]-apo A-I.
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.
authors.forename: Victoria
authors.initials: V
authors.lastname: López-Olmos
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.|Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Carreón-Torres
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.
authors.forename: María
authors.initials: M
authors.lastname: Luna-Luna
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.
authors.forename: Cristobal
authors.initials: C
authors.lastname: Flores-Castillo
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.
authors.forename: Miriam
authors.initials: M
authors.lastname: Martínez-Ramírez
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.|Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Rocío
authors.initials: R
authors.lastname: Bautista-Pérez
authors.affiliation: Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.|Nephrology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.affiliation: Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.|Cardiopulmonary Department, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Julio
authors.initials: J
authors.lastname: Sandoval-Zárate
authors.affiliation: Outpatient Care Department, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Francisco-Javier
authors.initials: FJ
authors.lastname: Roldán
authors.affiliation: Pathology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Alberto
authors.initials: A
authors.lastname: Aranda-Fraustro
authors.affiliation: Pathology Department, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Soria-Castro
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Muñoz-Vega
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.|Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: José-Manuel
authors.initials: JM
authors.lastname: Fragoso
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico.|Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico.
authors.forename: Gilberto
authors.initials: G
authors.lastname: Vargas-Alarcón
authors.affiliation: Molecular Biology Department, Instituto Nacional de Cardiología "Ignacio Chávez", Juan Badiano 1, Section XVI, 14080, México D.F., Mexico. opmendez@yahoo.com.|Atherosclerosis Study Group, Instituto Nacional de Cardiología "Ignacio Chávez", México D.F., Mexico. opmendez@yahoo.com.
authors.forename: Oscar
authors.initials: O
authors.lastname: Pérez-Méndez
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry / Q000378:metabolism*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D008075:Lipoproteins, HDL / Q000737:chemistry* / Q000378:metabolism*; D008297:Male; D010316:Particle Size; D011507:Proteinuria / Q000139:chemically induced* / Q000378:metabolism*; D011817:Rabbits
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D004317:Doxorubicin
keywords: Atherosclerosis; Coronary heart disease; HDL; Lipoprotein metabolism; Paraoxonase-1; Renal failure