Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis

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Santana, Monique F. M. ; Lira, Aecio L. A. ; Pinto, Raphael S. ; Minanni, Carlos A. ; Silva, Amanda R. M. ; Sawada, Maria I. B. A. C. ; Nakandakare, Edna R. ; Correa-Giannella, Maria L. C. ; Queiroz, Marcia S. ; Ronsein, Graziella E. ; Passarelli, Marisa

• Tipo de documento: Artigo Científico
• Fonte: LIPIDS IN HEALTH AND DISEASE; v. 19, n. 1, p. 14-pg., 2020-09-14.

Resumo

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 m(2)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 apoA-IV. 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(14)C-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. (AU)

• Processo FAPESP: 16/00696-3 - Compreendendo composição e função da HDL através de proteômica
• Beneficiário: Graziella Eliza Ronsein
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 18/00172-0 - Produtos de glicação avançada, estresse de retículo endoplasmático e modulação do transporte reverso de colesterol em artérias humanas com diferentes graus de Aterosclerose
• Beneficiário: Raphael de Souza Pinto
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 17/07725-1 - Proteômica: uma ferramenta para a investigação da composição e função da HDL em hiperlipidemia
• Beneficiário: Amanda Ribeiro Martins da Silva
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 16/15603-0 - Desvendando mecanismos envolvidos no controle glicêmico e nas complicações crônicas do Diabetes mellitus: contribuições à saúde humana
• Beneficiário: Ubiratan Fabres Machado
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 15/21072-5 - Influência do controle glicêmico ou do estágio da nefropatia sobre o transporte reverso de colesterol no Diabete melito: papel da memória metabólica induzida pela albumina modificada por glicação avançada
• Beneficiário: Marisa Passarelli
• Modalidade de apoio: Auxílio à Pesquisa - Regular