Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis
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...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Lipids in Health and Disease |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12944-020-01381-w |
| _version_ | 1818341764529913856 |
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| author | Monique F. M. Santana Aécio L. A. Lira Raphael S. Pinto Carlos A. Minanni Amanda R. M. Silva Maria I. B. A. C. Sawada Edna R. Nakandakare Maria L. C. Correa-Giannella Marcia S. Queiroz Graziella E. Ronsein Marisa Passarelli |
| author_facet | Monique F. M. Santana Aécio L. A. Lira Raphael S. Pinto Carlos A. Minanni Amanda R. M. Silva Maria I. B. A. C. Sawada Edna R. Nakandakare Maria L. C. Correa-Giannella Marcia S. Queiroz Graziella E. Ronsein Marisa Passarelli |
| author_sort | Monique F. M. Santana |
| collection | DOAJ |
| description | 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 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 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. |
| first_indexed | 2024-12-13T16:03:59Z |
| format | Article |
| id | doaj.art-ebf0943aee7e456cb8ae36880955d2ae |
| institution | Directory Open Access Journal |
| issn | 1476-511X |
| language | English |
| last_indexed | 2024-12-13T16:03:59Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Lipids in Health and Disease |
| spelling | doaj.art-ebf0943aee7e456cb8ae36880955d2ae2022-12-21T23:39:05ZengBMCLipids in Health and Disease1476-511X2020-09-0119111410.1186/s12944-020-01381-wEnrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysisMonique F. M. Santana0Aécio L. A. Lira1Raphael S. Pinto2Carlos A. Minanni3Amanda R. M. Silva4Maria I. B. A. C. Sawada5Edna R. Nakandakare6Maria L. C. Correa-Giannella7Marcia S. Queiroz8Graziella E. Ronsein9Marisa Passarelli10Laboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloLaboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloLaboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloLaboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloDepartamento de Bioquímica, Instituto de Química, Universidade de São PauloPrograma de Pós-Graduação em Medicina, Universidade Nove de JulhoLaboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloPrograma de Pós-Graduação em Medicina, Universidade Nove de JulhoPrograma de Pós-Graduação em Medicina, Universidade Nove de JulhoDepartamento de Bioquímica, Instituto de Química, Universidade de São PauloLaboratório de Lípides (LIM-10), Hospital das Clínicas (HCFMUSP) da Faculdade de Medicina da Universidade de São PauloAbstract 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 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 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.http://link.springer.com/article/10.1186/s12944-020-01381-wDiabetic kidney diseaseAdvanced glycationCarbamoylationHDLApolipoprotein A-IVApolipoprotein D |
| spellingShingle | Monique F. M. Santana Aécio L. A. Lira Raphael S. Pinto Carlos A. Minanni Amanda R. M. Silva Maria I. B. A. C. Sawada Edna R. Nakandakare Maria L. C. Correa-Giannella Marcia S. Queiroz Graziella E. Ronsein Marisa Passarelli Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis Lipids in Health and Disease Diabetic kidney disease Advanced glycation Carbamoylation HDL Apolipoprotein A-IV Apolipoprotein D |
| title | Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis |
| title_full | Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis |
| title_fullStr | Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis |
| title_full_unstemmed | Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis |
| title_short | Enrichment of apolipoprotein A-IV and apolipoprotein D in the HDL proteome is associated with HDL functions in diabetic kidney disease without dialysis |
| title_sort | enrichment of apolipoprotein a iv and apolipoprotein d in the hdl proteome is associated with hdl functions in diabetic kidney disease without dialysis |
| topic | Diabetic kidney disease Advanced glycation Carbamoylation HDL Apolipoprotein A-IV Apolipoprotein D |
| url | http://link.springer.com/article/10.1186/s12944-020-01381-w |
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