Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic
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(2020) 19:205
RESEARCH
Open Access
Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis Monique F. M. Santana1, Aécio L. A. Lira1, Raphael S. Pinto1,2, Carlos A. Minanni1,3, Amanda R. M. Silva4, Maria I. B. A. C. Sawada5, Edna R. Nakandakare1, Maria L. C. Correa-Giannella5,6, Marcia S. Queiroz5, Graziella E. Ronsein4 and Marisa Passarelli1,5*
Abstract Background and aims: Diabetic kidney disease (DKD) is associated with lipid derangements that worsen kidney function and enhance cardiovascular (CVD) risk. The management of dyslipidemia, hypertension and other traditional risk factors does not completely prevent CVD complications, bringing up the participation of nontraditional risk factors such as advanced glycation end products (AGEs), carbamoylation and changes in the HDL proteome and functionality. The HDL composition, proteome, chemical modification and functionality were analyzed in nondialysis subjects with DKD categorized according to the estimated glomerular filtration rate (eGFR) and urinary albumin excretion rate (AER). Methods: Individuals with DKD were divided into eGFR> 60 mL/min/1.73 m2 plus AER stages A1 and A2 (n = 10) and eGFR< 60 plus A3 (n = 25) and matched by age with control subjects (eGFR> 60; n = 8). Results: Targeted proteomic analyses quantified 28 proteins associated with HDL in all groups, although only 2 were more highly expressed in the eGFR< 60 + A3 group than in the controls: apolipoprotein D (apoD) and apoAIV. HDL from the eGFR< 60 + A3 group presented higher levels of total AGEs (20%), pentosidine (6.3%) and carbamoylation (4.2 x) and a reduced ability to remove 14C-cholesterol from macrophages (33%) in comparison to HDL from controls. The antioxidant role of HDL (lag time for LDL oxidation) was similar among groups, but HDL from the eGFR< 60 + A3 group presented a greater ability to inhibit the secretion of IL-6 and TNF-alpha (95%) in LPS-elicited macrophages in comparison to the control group. Conclusion: The increase in apoD and apoA-IV could contribute to counteracting the HDL chemical modification by AGEs and carbamoylation, which contributes to HDL loss of function in well-established DKD. Keywords: Diabetic kidney disease, Advanced glycation, Carbamoylation, HDL, Apolipoprotein A-IV, Apolipoprotein D, Proteomics, Atherosclerosis * Correspondence: [email protected]; [email protected] 1 Laboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Arnaldo 455, room 3305; CEP, São Paulo 01246-000, Brazil 5 Programa de Pós-Graduação em Medicina, Universidade Nove de Julho, São Paulo, Brazil Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropria
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